fbpx
维基百科

长链非编码核糖核酸

六月 30, 2023

长链非编码核糖核酸（英語：long non-coding RNAs，简称为lncRNA）指的是长于200核苷酸的不编码蛋白质的转录物（Perkel 2013）。该有些武断的界定将长链非编码核糖核酸与较小的调控核糖核酸区分开来，后者如微核糖核酸（miRNAs）、小干扰核糖核酸（siRNAs）、Piwi互作核糖核酸类（piRNAs）、小核仁核糖核酸（snoRNAs）及其它短核糖核酸（Ma 2013）。

长链非编码核糖核酸的丰度

近年研究显示人类基因组中的转录只有五分之一与蛋白编码基因有关（Kapranov 2007），这说明至少有较编码核糖核酸序列四倍多的长链非编码核糖核酸。而像FANTOM（哺乳动物cDNA功能注释）等的大规模互补脱氧核糖核酸（cDNA）测序计划揭示了转录的复杂性（Carninci 2005）。FANTOM3计划从约一万个不同的基因座中鉴定出了约三万五千条非编码转录物它们有着与mRNA类类似的特征，包括5'端有帽、受到剪接及多聚腺苷酸化，但只有很小的開放閱讀框（ORF）或根本没有（Carninci 2005）。然而长链非编码RNA的丰度是意料之外的，其数目代表的是保守估计的最低值，因为这种方法忽略了许多单独的转录物及非多腺苷酸化的转录物（瓦片阵列数据显示出40%以上的转录物是非多腺苷酸化的）（Cheng 2005）。尽管如此，在这些cDNA文库中明确鉴定非编码RNA类仍是充满挑战的，因为该方法无法区分非编码转录物及蛋白编码转录物。

长链非编码核糖核酸的基因组组织

目前将哺乳动物基因组的全景描绘为：长段的基因间空间将多个转录“焦点”分割开（Carninci 2005）。然而长链非编码核糖核酸正位于这些基因间区段中并由此转录出来，其中大多数是与其它转录物之间呈错综复杂的正义或反义重叠，这些转录物往往包括了蛋白编码基因（Kapranov 2007）。在正义或反义链上的多个不同的编码或非编码转录物共享这些转录焦点中的基因组序列（Birney 2007），使得这些重叠的亚型之间产生复杂的层次结构。例如，8961个cDNA中的3012个曾被FANTOM2计划注释为编码序列中的一段截短序列，但后来又重新被指定为蛋白编码cDNA中的新非编码RNA变异体（Carninci 2005）。尽管编码RNA及非编码RNA的交错排列具备一定的丰度和保守性，并可能意味着它们两者之间具有某些生物学关联性，但仍无法对这些复杂的焦点结构进行简单的评价。

GENCODE共同体已综合性整理及分析了一些人类长链非编码RNA的注释及它们的基因组结构、修饰、细胞定位及组织表达谱（Derrien 2012）。他们的分析结果说明人类长链非编码RNA易形成具有两个外显子的转录物（Derrien 2012）。

长链非编码核糖核酸的保守性

如微核糖核酸及小核仁核糖核酸等的众多小型核糖核酸都显现出了跨多物种的保守性（Bentwich 2005）。与之相反，大多数长链非编码核糖核酸则保守性不强，这一点常被引用为其不具备功能的证据（Brosius 2005；Struhl 2007）。然而，如Air及Xist等经过详细研究的长链非编码RNA，它们的保守性也很差（Nesterova 2001），这意味着非编码RNA类可能受到不同的选择压力（Pang 2006）。mRNA必须保守密码子的正常用法并防止单个长ORF中出现移码突变，然而对长链非编码RNA的选择压力可能只会令其保守其中的较短区域，这些较短区域对于结构或序列特异性相互作用较为关键。因此，我们可见选择压力只会作用于长链非编码RNA转录物的小块区域。仍然要看到：尽管长链非编码RNA总体来说保守性较低，但仍可见许多长链非编码RNA具有较强的保守元件。例如，高度保守的phastCons元件中有19%存在于已知的内含子中，而其它32%存在于未注释的区域之中（Siepel 2005）。此外，人类长链非编码RNA中的具有代表性的一类长链非编码RNA在碱基取代和插入/缺失速率方面显现出较小但显著的降低，这一现象指示了净化选择压力使得转录物的完整性得到保守，这在序列、启动子及剪接三种水平上体现出来（Ponjavic 2007）。

非编码核糖核酸的保守性差可能是近期且快速的适应性选择的结果。例如，非编码核糖核酸较蛋白编码基因可能对进化压力可塑性更强，如Xist或Air等的许多世系特异性非编码RNA的存在可以证明这一点（Pang 2006）。相对于黑猩猩基因组来说人类基因组中经受近期进化改变的保守区域确实主要存在于非编码区域，其中很多已有详尽描述（Pollard 2006；Pollard 2006）。其中包括一条名为HAR1F的非编码RNA，该基因在人类中经历了快速的进化变化，且特异性地在人类新皮质的卡哈尔-雷济厄斯氏细胞中特异性表达（Pollard 2006）。现有报道称许多功能已确定的RNA进化速率也很快（Pang 2006；Smith 2004），这可能由于这些序列受到结构-功能约束时表现得更灵活，我们可以期待在这些序列中发现新的进化方式。人类基因组中有数千条序列的一级序列保守性较差，但有证据显示它们RNA二級結構却存在着保守性（Torarinsson 2006；Torarinsson 2008），这支持了上述论点。

长链非编码核糖核酸的功能

cDNA文库的大规模测序及更先进的基于下一代测序的转录组测序表明哺乳动物中长链非编码核糖核酸的数量大约是几万条。然而，虽然越来越多的证据提示大多数长链非编码核糖核酸具有功能（Mercer 2009；Dinger 2009），但相对只有一小部分已被证明有生物学重大意义。截至2012年十二月，约有127条长链非编码RNA在LncRNAdb（一个描述长链非编码RNA的文献数据库）中有功能注释（Amral 2011）。

长链非编码RNA类在基因转录调控中的作用

长链非编码RNA类在基因特异性转录中的作用

RNA转录在真核生物中是一个受到严密调控的过程。非编码RNA可以靶向该进程的多个方面，包括靶向转录激活因子或转录抑制因子、如RNA聚合酶（RNAP）Ⅱ等转录反应中的各组分、甚至是DNA双螺旋结构，以达到调控基因转录及表达的目的（Goodrich 2006）。非编码RNA将这些机制结合在一起可以组成为一个包括转录因子在内的调控网络，可以精细地调控复杂真核生物的基因表达。

非编码RNA通过多种不同的机制调节转录因子的功能，包括充当共调控因子的角色、修饰转录因子的活性或是调控共调控因子的活性。例如，非编码RNA Evf-2作为同源异形框转录因子Dlx2的共激活因子，Dlx2在前脑发育及神经发生中起到重要作用（Feng 2006；Panganiban 2002）。Evf-2转录自位于Dlx5与Dlx6基因之间的超保守元件，音猬因子在前脑发育过程中诱导该长链的转录（Feng 2006）。Evf-2接着将Dlx2转录因子招募到同一个超保守元件处，Dlx2在此处诱导Dlx5的表达。哺乳动物基因组中存在其它一些可转录且执行增强子功能的超级保守或高度保守元件，这提示Evf-2可作为范例阐述脊椎动物生长过程中以复杂表达的形式严密调控重要发育基因的普遍机制（Pennacchio 2006；Visel 2008）。近期研究也确实发现与之类似的其它非编码超保守元件的转录及表达在人类白血病中出现异常，且促进结肠癌细胞的凋亡，这提示了它们涉及到肿瘤形成（Calin 2007）。

局部的非编码RNA类可以招募转录机制对附近蛋白编码基因的转录加以调控。TLS（英語：translocated in liposarcoma）是一种结合RNA的蛋白，它结合到CREB结合蛋白和组蛋白乙酰基转移酶p300上并抑制这两者在靶基因周期蛋白D1上的活性，从而起到抑制后者的作用。作为DNA受损信号的响应，长链非编码RNA以低水平表达出来并拴在周期蛋白D1基因的5'调控区域上，这指导了TLS招募到周期蛋白D1启动子上（Wang 2008）。除此之外，这些局部的非编码RNA作为配体调控TLS的活性。从更广泛的层面上说，这一机制使得细胞可以利用RNA结合蛋白（它们组成了哺乳动物蛋白质组中的最庞大的种类之一）并在转录程序控制中整合它们的功能。

在X染色体失活的情况下一些基因仍可以转录，近期对逃避染色体失活控制的染色体区域进行研究，发现其中表达的长链非编码RNA可能介导了这一过程（Reinius 2010）。

长链非编码RNA调控基础转录机器

非编码RNA还可以靶向通用转录因子，后者是RNAPⅡ转录所有基因所必需的（Goodrich 2006）。这些通用因子包括了起始复合体中组装在启动子上或涉及转录延伸的部件。转录自二氢叶酸还原酶（DHFR）基因上游次要启动子的一条非编码RNA进入DHFR主要启动子，形成稳定的RNA-DNA三股螺旋以阻止转录辅因子TFⅡB结合到其上（Martianov 2007）。已知真核染色体上存在着数千个三股螺旋（Lee 1987），这一调控基因表达的新机制可能事实上代表这些三股螺旋在控制启动子上起到的广泛作用。U1非编码RNA通过结合到TFⅡH上并刺激其对RNAPⅡ的C-端以实现诱导转录起始（Kwek 2002）。相反，非编码RNA 7SK可通过下列方式起到抑制转录延伸的作用：7SK首先与HEXIM1/2结合，形成抑制性复合物，该复合物阻止PTEFb通用转录因子去磷酸化RNAPⅡ的C-端结构域（Kwek 2002；Yang 2001；Yik 2003），当细胞处于应激状况下可以抑制全局延伸。这些例子中的机制可以绕开单个启动子上特异性的调控模式，介导起始及延伸转录机器工作水平发生直接改变，提供了迅速影响基因表达全局改变的方法。

现也证明非编码重复序列有着介导全局调控的能力。人类的短散在核内（SINE）Alu元件及小鼠中同源的B1和B2元件是基因组中丰度最高的可移动性元件，分别组成了人类和小鼠基因组的约10%和约6%（Lander 2001；Waterston 2002）。在如热休克等环境应激情况下这些元件被RNAPⅢ转录为非编码RNA（Liu 1995），后者接下来会以高亲和度的方式与RNAPⅡ结合并阻止其形成为有活性的前起始复合物（Allen 2004；Espinoza 2004；Espinoza 2007；Mariner & Walters 2008）。这使得在响应应激的情况下可以大范围并迅速抑制基因的表达（Allen 2004；Mariner & Walters 2008）。

对Alu元件的RNA转录物中的功能序列进行分析后，发现其亦有类似于蛋白质转录因子中结构域的模块化结构（Shamovsky 2008）。Alu元件RNA包括两个“臂”，每个臂都可以结合到一个RNAPⅡ分子上；体外实验表明该RNA还具有两个调控结构域，起到抑制RNAPⅡ转录活性的作用（Mariner 2008）。 These two loosely-structured domains may even be concatenated to other ncRNAs such as B1 elements to impart their repressive role (Mariner & Walters 2008). The abundance and distribution of Alu elements and similar repetitive elements throughout the mammalian genome may be partly due to these functional domains being co-opted into other long ncRNAs during evolution, with the presence of functional repeat sequence domains being a common characteristic of several known long ncRNAs including Kcnq1ot1, Xlsirt and Xist (Mattick 2003; Mohammad 2008; Wutz 2002; Zearfoss 2003).

除了热休克外，如病毒感染、, the expression of SINE elements (including Alu, B1, and B2 RNAs) increases during cellular stress such as viral infection (Singh 1985) in some cancer cells (Tang 2005) where they may similarly regulate global changes to gene expression. The ability of Alu and B2 RNA to bind directly to RNAP II provides a broad mechanism to repress transcription (Espinoza 2004; Mariner & Walters 2008). Nevertheless, there are specific exceptions to this global response where Alu or B2 RNAs are not found at activated promoters of genes undergoing induction, such as the heat shock genes (Mariner & Walters 2008). This additional hierarchy of regulation that exempts individual genes from the generalised repression also involves a long ncRNA, heat shock RNA-1 (HSR-1). It was argued that HSR-1 is present in all cells in an inactive state, but upon stress is activated to induce the expression of heat shock genes (Shamovsky 2006). The authors found that this activation involves a conformational alteration to the structure of HSR-1 in response to rising temperatures, thereby permitting its interaction with the transcriptional activator HSF-1 that subsequently undergoes trimerisation and induces the expression of heat shock genes (Shamovsky 2006). In the broad sense, these examples illustrate a regulatory circuit nested witin ncRNAs whereby Alu or B2 RNAs repress general gene expression, while other ncRNAs activate the expression of specific genes.

长链非编码RNA类在基因转录后调控中的作用

除了在转录水平上调控，ncRNAs 也在转录后水平调控mRNA加工的不同方面。与小调控RNAs，例如微小RNAs和小核仁RNAs，类似，ncRNAs 的功能包括与目标mRNA进行互补碱基配对。互补ncRNA和mRNA形成的RNA双链可能为需要结合反式作用因子的mRNA募集关键因子，可能影响转录后水平基因表达的每一步，包括前体mRNA加工，剪接，运输，翻译以及降解。

长链非编码RNA类在剪接调控中的作用

The splicing of mRNA can induce its translation and functionally diversify the repertoire of proteins it encodes. The Zeb2 mRNA, which has a particularly long 5’UTR, requires the retention of a 5’UTR intron that contains an internal ribosome entry site for efficient translation (Beltran 2008). However, retention of the intron is dependent on the expression of an antisense transcript that complements the intronic 5’ splice site (Beltran 2008). Therefore, the ectopic expression of the antisense transcript represses splicing and induces translation of the Zeb2 mRNA during mesenchymal development. Likewise, the expression of an overlapping antisense Rev-ErbAα2 transcript controls the alternative splicing of the thyroid hormone receptor ErbAα2 mRNA to form two antagonistic isoforms (Munroe 1991).

长链非编码RNA类在翻译调控中的作用

NcRNA may also apply additional regulatory pressures during translation, a property particularly exploited in neurons where the dendritic or axonal translation of mRNA in response to synaptic activity contributes to changes in synaptic plasticity and the remodelling of neuronal networks. The RNAP III transcribed BC1 and BC200 ncRNAs, that previously derived from tRNAs, are expressed in the mouse and human central nervous system, respectively (Tiedge 1993; Tiedge 1991). BC1 expression is induced in response to synaptic activity and synaptogenesis and is specifically targeted to dendrites in neurons (Muslimov 1998). Sequence complementarity between BC1 and regions of various neuron-specific mRNAs also suggest a role for BC1 in targeted translational repression (Wang 2005). Indeed it was recently shown that BC1 is associated with translational repression in dendrites to control the efficiency of dopamine D2 receptor-mediated transmission in the striatum (Centonze 2007) and BC1 RNA-deleted mice exhibit behavioural changes with reduced exploration and increased anxiety (Lewejohann 2004).

长链非编码RNA类在siRNA导向的基因调控中的作用

In addition to masking key elements within single-stranded RNA, the formation of double-stranded RNA duplexes can also provide a substrate for the generation of endogenous siRNAs (endo-siRNAs) in Drosophila and mouse oocytes (Golden 2008). The annealing of complementary sequences, such as antisense or repetitive regions between transcripts, forms an RNA duplex that may be processed by Dicer-2 into endo-siRNAs. Also, long ncRNAs that form extended intramolecular hairpins may be processed into siRNAs, compellingly illustrated by the esi-1 and esi-2 transcripts (Czech 2008). Endo-siRNAs generated from these transcripts seem particularly useful in suppressing the spread of mobile transposon elements within the genome in the germline. However, the generation of endo-siRNAs from antisense transcripts or pseudogenes may also silence the expression of their functional counterparts via RISC effector complexes, acting as an important node that integrates various modes of long and short RNA regulation, as exemplified by the Xist and Tsix (see above) (Ogawa 2008).

长链非编码RNA类在表观遗传调控中的作用

包括组蛋白和DNA甲基化、组蛋白乙酰化和SUMO化等在内的表观遗传修饰影响了染色体生物学的众多方面，主要包括通过对广大染色质区域进行重塑从而调控大量基因（Kiefer 2007；Mikkelsen 2007）。一段时间以来，RNA作为染色质的有机组成部分已被人知晓（Nickerson 1989；Rodriguez-Campos 2007），但现在我们才开始认识到RNA在涉及到染色质修饰通路上的意义（Chen 2008；Rinn 2007；Sanchez-Elsner 2006）。

果蝇属中的长链非编码RNA类通过将三胸蛋白Ash1募集到同源异形调控元件并指导其发挥染色质修饰作用的方式诱导同源异形基因Ubx的表达（Sanchez-Elsner 2006）。后来发现哺乳动物中也存在着相似的调控模式：认为强大的表观遗传机制奠定了胚胎同源异形基因家族的表达谱，而同源异形基因家族是贯穿整个人体发育过程中持续发挥作用的重要因子（Mazo 2007；Rinn 2007）。人类同源异形基因家族确实与数百个非编码RNA之间有着相关性，这些非编码RNA在人体发育的时空轴上按顺序表达，这些非编码RNA也定义染色质各区域中组蛋白甲基化程度的差异以及RNA聚合酶可进入染色质的程度（Rinn 2007）。其中一条名为HOTAIR的转录自HOXC基因座的非编码RNA通过改变组蛋白三甲基化状态从而使HOXD基因座中长约40kb的区域发生转录沉默。目前认为HOTAIR执行的作用机制是：多梳染色质重塑复合物具有操纵细胞表观遗传状态的功能，而HOTAIR以反式调控的方式指导该功能的发挥并继而影响基因的表达。多梳复合物中的成员包括SUZ12、EZH2和EED等，它们具有RNA结合结构域并可能结合HOTAIR及其它类似的非编码RNA类（Denisenko 1998；Katayama 2005）。该例子极好地描绘出了这样一个更广泛的主题：非编码RNA类招募一系列染色质修饰蛋白到特定基因组基因座上并发挥功能，这更加突出了目前所绘制基因组图谱的复杂性（Mikkelsen 2007）。发育时期中调控基因表达的染色质修饰有着区域化的模式，大量长链非编码与蛋白编码基因的联系确实帮助塑造了这种模式。例如，大多数蛋白编码基因都具有配对的反义基因，许多抑癌基因在癌症中常受到沉默，一些反义基因使用表观遗传机制使这些抑癌基因沉默（Yu 2008）。近期研究发现：在白血病中p15基因和一条反义非编码RNA的表达此消彼长（Yu 2008）。经过详细分析发现：p15的反义非编码RNA（CDKN2BAS）可通过一种未知机制诱导p15的异染色质和DNA甲基化状态发生改变，因而调控了p15基因的表达（Yu 2008）。因此，相关的反义非编码RNA类表达发生异常可能继而沉默了抑癌基因，从而走向癌症发生。

基因印记

最近非编码RNA指导的染色质修饰主题最初是从基因组印记的现象中引出的，基因组印记是仅从母系或父系染色体两者中的一个表达出等位基因的现象。一般来说，印记基因是呈簇状排列于染色体上，这提示：印记的机制是作用于局部的染色质区域上而不是针对单个基因。这些基因簇常常与长链非编码RNA相关：长链非编码RNA的表达量与在相同等位上相连锁的蛋白编码基因受到抑制的程度呈正相关（Pauler 2007）。详细分析确实显示出非编码RNA Kcnqot1和Igf2r/Air在指导基因印记上发挥着重要作用（Braidotti 2004）。

几乎所有位于Kcnq1基因座Almost all the genes at the Kcnq1 loci are maternally inherited, except the paternally expressed antisense ncRNA Kcnqot1 (Mitsuya 1999). Transgenic mice with truncated Kcnq1ot fail to silence the adjacent genes, suggesting that Kcnqot1 is crucial to the imprinting of genes on the paternal chromosome (Mancini-Dinardo 2006). It appears that Kcnqot1 is able to direct the trimethylation of lysine 9 (H3K9me3) and 27 of histone 3 (H3K27me3) to an imprinting centre that overlaps the Kcnqot1 promoter and actually resides within a Kcnq1 sense exon (Umlauf 2004). Similar to HOTAIR (see above), Eed-Ezh2 Polycomb complexes are recruited to the Kcnq1 loci paternal chromosome, possibly by Kcnqot1, where they may mediate gene silencing through repressive histone methylation (Umlauf 2004). A differentially methylated imprinting centre also overlaps the promoter of a long antisense ncRNA Air that is responsible for the silencing of neighbouring genes at the Igf2r locus on the paternal chromosome (Sleutels 2002; Zwart 2001). The presence of allele-specific histone methylation at the Igf2r locus suggests Air also mediates silencing via chromatin modification (Fournier 2002).

Xist与X-染色体失活

The inactivation of a X-chromosome in female placental mammals is directed by one of the earliest and best characterized long ncRNAs, Xist (Wutz 2007). The expression of Xist from the future inactive X-chromosome, and its subsequent coating of the inactive X-chromosome, occurs during early embryonic stem cell differentiation. Xist expression is followed by irreversible layers of chromatin modifications that include the loss of the histone (H3K9) acetylation and H3K4 methylation that are associated with active chromatin, and the induction of repressive chromatin modifications including H4 hypoacetylation, H3K27 trimethylation (Wutz 2007), H3K9 hypermethylation and H4K20 monomethylation as well as H2AK119 monoubiquitylation. These modifications coincide with the transcriptional silencing of the X-linked genes (Morey 2004). Xist RNA also localises the histone variant macroH2A to the inactive X–chromosome (Costanzi 1998). There are additional ncRNAs that are also present at the Xist loci, including an antisense transcript Tsix, which is expressed from the future active chromosome and able to repress Xist expression by the generation of endogenous siRNA (Ogawa 2008). Together these ncRNAs ensure that only one X-chromosome is active in female mammals.

端粒非编码RNA类

Telomeres form the terminal region of mammalian chromosomes and are essential for stability and aging and play central roles in diseases such as cancer (Blasco 2007). Telomeres have been long considered transcriptionally inert DNA-protein complexes until it was recently shown that telomeric repeats may be transcribed as telomeric RNAs (TelRNAs) (Schoeftner 2008) or telomeric repeat-containing RNAs (Azzalin 2007). These ncRNAs are heterogeneous in length, transcribed from several sub-telomeric loci and physically localise to telomeres. Their association with chromatin, which suggests an involvement in regulating telomere specific heterochromatin modifications, is repressed by SMG proteins that protect chromosome ends from telomere loss (Azzalin 2007). In addition, TelRNAs block telomerase activity in vitro and may therefore regulate telomerase activity (Schoeftner 2008). Although early, these studies suggest an involvement for telomeric ncRNAs in various aspects of telomere biology.

长链非编码RNA类在衰老与疾病中的作用

外部链接

  • LncRNAWiki （页面存档备份，存于互联网档案馆）: a wiki-based database for management of human lncRNAs.
  • ChIPBase database[永久失效連結]: decodes the transcriptional regulation of lncRNAs from ChIP-Seq and provides expression profiles of lncRNAs (lincRNAs) from RNA-Seq data across 22 tissues.
  • lncRNAdb database （页面存档备份，存于互联网档案馆）: providing comprehensive annotations of functional long non-coding RNAs (lncRNAs).
  • Long RNA Synthesis （页面存档备份，存于互联网档案馆）: chemical long RNA synthesis and long RNA synthesis by transcription.

另见

参考文献

  • Allen E, Xie Z, Gustafson AM, Sung GH, Spatafora JW, Carrington JC. Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana. Nature Genetics. December 2004, 36 (12): 1282–90. PMID 15565108. doi:10.1038/ng1478. 
  • PMID 21112873
  • Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J. Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science. November 2007, 318 (5851): 798–801. Bibcode:2007Sci...318..798A. PMID 17916692. doi:10.1126/science.1147182. 
  • Beltran M, Puig I, Peña C; et al. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes & Development. March 2008, 22 (6): 756–69. PMC 2275429  . PMID 18347095. doi:10.1101/gad.455708. 
  • Bentwich I, Avniel A, Karov Y; et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nature Genetics. July 2005, 37 (7): 766–70. PMID 15965474. doi:10.1038/ng1590. 
  • Birney E, Stamatoyannopoulos JA, Dutta A; et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. June 2007, 447 (7146): 799–816. Bibcode:2007Natur.447..799B. PMC 2212820  . PMID 17571346. doi:10.1038/nature05874. 
  • Blasco MA. Telomere length, stem cells and aging. Nature Chemical Biology. October 2007, 3 (10): 640–9. PMID 17876321. doi:10.1038/nchembio.2007.38. 
  • Braidotti G, Baubec T, Pauler F; et al. The Air noncoding RNA: an imprinted cis-silencing transcript. Cold Spring Harbor Symposia on Quantitative Biology. 2004, 69: 55–66. PMID 16117633. doi:10.1101/sqb.2004.69.55. 
  • Broadbent HM, Peden JF, Lorkowski S; et al. Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRIL locus on chromosome 9p. Human Molecular Genetics. 2008, 17 (6): 806–14. PMID 18048406. doi:10.1093/hmg/ddm352. 
  • Brosius J. Waste not, want not--transcript excess in multicellular eukaryotes. Trends in Genetics. May 2005, 21 (5): 287–8. PMID 15851065. doi:10.1016/j.tig.2005.02.014. 
  • Calin GA, Liu CG, Ferracin M; et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell. September 2007, 12 (3): 215–29. PMID 17785203. doi:10.1016/j.ccr.2007.07.027. 
  • Carninci P, Kasukawa T, Katayama S; et al. The transcriptional landscape of the mammalian genome. Science. September 2005, 309 (5740): 1559–63. Bibcode:2005Sci...309.1559F. PMID 16141072. doi:10.1126/science.1112014. 
  • Centonze D, Rossi S, Napoli I; et al. The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum. The Journal of Neuroscience. August 2007, 27 (33): 8885–92. PMID 17699670. doi:10.1523/JNEUROSCI.0548-07.2007. 
  • Chen X, Xu H, Yuan P; et al. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell. June 2008, 133 (6): 1106–17. PMID 18555785. doi:10.1016/j.cell.2008.04.043. 
  • Cheng J, Kapranov P, Drenkow J; et al. Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science. May 2005, 308 (5725): 1149–54. Bibcode:2005Sci...308.1149C. PMID 15790807. doi:10.1126/science.1108625. 
  • Costanzi C, Pehrson JR. Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature. June 1998, 393 (6685): 599–601. Bibcode:1998Natur.393..599C. PMID 9634239. doi:10.1038/31275. 
  • Czech B, Malone CD, Zhou R; et al. An endogenous small interfering RNA pathway in Drosophila. Nature. June 2008, 453 (7196): 798–802. Bibcode:2008Natur.453..798C. PMID 18463631. doi:10.1038/nature07007. 
  • Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K. . Molecular and Cellular Biology. 1 October 1998, 18 (10): 5634–42 [2014-02-01]. PMC 109149  . PMID 9742080. （原始内容存档于2019-07-10）. 
  • PMID 22955988
  • Dieci G, Fiorino G, Castelnuovo M, Teichmann M, Pagano A. The expanding RNA polymerase III transcriptome. Trends in Genetics. December 2007, 23 (12): 614–22. PMID 17977614. doi:10.1016/j.tig.2007.09.001. 
  • PMID 19770204
  • Eis PS, Tam W, Sun L; et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proceedings of the National Academy of Sciences of the United States of America. March 2005, 102 (10): 3627–32. Bibcode:2005PNAS..102.3627E. PMC 552785  . PMID 15738415. doi:10.1073/pnas.0500613102. 
  • Espinoza CA, Allen TA, Hieb AR, Kugel JF, Goodrich JA. B2 RNA binds directly to RNA polymerase II to repress transcript synthesis. Nature Structural & Molecular Biology. September 2004, 11 (9): 822–9. PMID 15300239. doi:10.1038/nsmb812. 
  • Espinoza CA, Goodrich JA, Kugel JF. Characterization of the structure, function, and mechanism of B2 RNA, an ncRNA repressor of RNA polymerase II transcription. RNA. April 2007, 13 (4): 583–96. PMC 1831867  . PMID 17307818. doi:10.1261/rna.310307. 
  • Faghihi MA, Modarresi F, Khalil AM; et al. Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nature Medicine. July 2008, 14 (7): 723–30. PMC 2826895  . PMID 18587408. doi:10.1038/nm1784. 
  • Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes & Development. June 2006, 20 (11): 1470–84. PMC 1475760  . PMID 16705037. doi:10.1101/gad.1416106. 
  • Fournier C, Goto Y, Ballestar E; et al. Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes. The EMBO Journal. December 2002, 21 (23): 6560–70. PMC 136958  . PMID 12456662. doi:10.1093/emboj/cdf655. 
  • Fu X, Ravindranath L, Tran N, Petrovics G, Srivastava S. Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, PCGEM1. DNA and Cell Biology. March 2006, 25 (3): 135–41. PMID 16569192. doi:10.1089/dna.2006.25.135. 
  • Golden DE, Gerbasi VR, Sontheimer EJ. An inside job for siRNAs. Molecular Cell. August 2008, 31 (3): 309–12. PMC 2675693  . PMID 18691963. doi:10.1016/j.molcel.2008.07.008. 
  • Goodrich JA, Kugel JF. Non-coding-RNA regulators of RNA polymerase II transcription. Nature Reviews Molecular Cell Biology. August 2006, 7 (8): 612–6. PMID 16723972. doi:10.1038/nrm1946. 
  • Hesman Saey, Tina. . Science News. 17 December 2011, 180 (13): 22–25 [2014-02-01]. （原始内容存档于2013-07-27）. 
  • Ishii N, Ozaki K, Sato H; et al. Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. Journal of Human Genetics. 2006, 51 (12): 1087–99. PMID 17066261. doi:10.1007/s10038-006-0070-9. 
  • Jarinova O, Stewart AF, Roberts R; et al. Functional analysis of the chromosome 9p21.3 coronary artery disease risk locus. Arteriosclerosis, Thrombosis, and Vascular Biology. October 2009, 29 (10): 1671–77. PMID 19592466. doi:10.1161/ATVBAHA.109.189522. 
  • Kapranov P, Cheng J, Dike S; et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science. June 2007, 316 (5830): 1484–8. Bibcode:2007Sci...316.1484K. PMID 17510325. doi:10.1126/science.1138341. 
  • Kapranov P, Willingham AT, Gingeras TR. Genome-wide transcription and the implications for genomic organization. Nature Reviews. Genetics. June 2007, 8 (6): 413–23. PMID 17486121. doi:10.1038/nrg2083. 
  • Kapranov P, St Laurent G, Raz T; et al. . BMC Biol. 2010, 8: 149 [2014-02-01]. PMC 3022773  . PMID 21176148. doi:10.1186/1741-7007-8-149. （原始内容存档于2015-11-02）.  Erratum in: BMC Biol. 2011;9:86.
  • Katayama S, Tomaru Y, Kasukawa T; et al. Antisense transcription in the mammalian transcriptome. Science. September 2005, 309 (5740): 1564–6. Bibcode:2005Sci...309.1564R. PMID 16141073. doi:10.1126/science.1112009. 
  • Kiefer JC. Epigenetics in development. Developmental Dynamics. April 2007, 236 (4): 1144–56. PMID 17304537. doi:10.1002/dvdy.21094. 
  • Kim. Evidence for bacterial origin of heat shock RNA-1. RNA. February 2010, 16 (2): 274–279. PMC 2811656  . PMID 20040589. doi:10.1261/rna.1879610. 
  • Kwek KY, Murphy S, Furger A; et al. U1 snRNA associates with TFIIH and regulates transcriptional initiation. Nature Structural Biology. November 2002, 9 (11): 800–5. PMID 12389039. doi:10.1038/nsb862. 
  • Lander ES, Linton LM, Birren B; et al. Initial sequencing and analysis of the human genome. Nature. February 2001, 409 (6822): 860–921. PMID 11237011. doi:10.1038/35057062. 
  • Lee JS, Burkholder GD, Latimer LJ, Haug BL, Braun RP. A monoclonal antibody to triplex DNA binds to eucaryotic chromosomes. Nucleic Acids Research. February 1987, 15 (3): 1047–61. PMC 340507  . PMID 2434928. doi:10.1093/nar/15.3.1047. 
  • Lewejohann L, Skryabin BV, Sachser N; et al. Role of a neuronal small non-messenger RNA: behavioural alterations in BC1 RNA-deleted mice. Behavioural Brain Research. September 2004, 154 (1): 273–89. PMID 15302134. doi:10.1016/j.bbr.2004.02.015. 
  • Li J, Witte DP, Van Dyke T, Askew DS. Expression of the putative proto-oncogene His-1 in normal and neoplastic tissues. The American Journal of Pathology. April 1997, 150 (4): 1297–305. PMC 1858164  . PMID 9094986. 
  • Lin R, Maeda S, Liu C, Karin M, Edgington TS. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene. February 2007, 26 (6): 851–8. PMID 16878148. doi:10.1038/sj.onc.1209846. 
  • lincRNA homepage of the Rinn Lab （页面存档备份，存于互联网档案馆）
  • Liu WM, Chu WM, Choudary PV, Schmid CW. Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts. Nucleic Acids Research. May 1995, 23 (10): 1758–65. PMC 306933  . PMID 7784180. doi:10.1093/nar/23.10.1758. 
  • Liu Y, Sanoff HK, Cho H; et al. INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis. PloS One. April 2009, 4 (4): e5027. Bibcode:2009PLoSO...4.5027L. PMC 2660422  . PMID 19343170. doi:10.1371/journal.pone.0005027. 
  • Mancini-Dinardo D, Steele SJ, Levorse JM, Ingram RS, Tilghman SM. Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes & Development. May 2006, 20 (10): 1268–82. PMC 1472902  . PMID 16702402. doi:10.1101/gad.1416906. 
  • Mariner PD, Walters RD, Espinoza CA; et al. Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Molecular Cell. February 2008, 29 (4): 499–509. PMID 18313387. doi:10.1016/j.molcel.2007.12.013. 
  • Martianov I, Ramadass A, Serra Barros A, Chow N, Akoulitchev A. Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature. February 2007, 445 (7128): 666–70. PMID 17237763. doi:10.1038/nature05519. 
  • Mattick JS. Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. BioEssays. October 2003, 25 (10): 930–9. PMID 14505360. doi:10.1002/bies.10332. 
  • Mazo A, Hodgson JW, Petruk S, Sedkov Y, Brock HW. Transcriptional interference: an unexpected layer of complexity in gene regulation. Journal of Cell Science. August 2007, 120 (Pt 16): 2755–61. PMID 17690303. doi:10.1242/jcs.007633. 
  • McPherson R, Pertsemlidis A, Kavaslar N ; et al. A Common Allele on Chromosome 9 Associated with Coronary Heart Disease. Science. May 2007, 316 (5830): 1488–91. Bibcode:2007Sci...316.1488M. PMC 2711874  . PMID 17478681. doi:10.1126/science.1142447. 
  • PMID 19188922
  • Mikkelsen TS, Ku M, Jaffe DB; et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. August 2007, 448 (7153): 553–60. Bibcode:2007Natur.448..553M. PMC 2921165  . PMID 17603471. doi:10.1038/nature06008. 
  • Mitsuya K, Meguro M, Lee MP; et al. LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids. Human Molecular Genetics. July 1999, 8 (7): 1209–17. PMID 10369866. doi:10.1093/hmg/8.7.1209. 
  • Mohammad F, Pandey RR, Nagano T; et al. Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region. Molecular and Cellular Biology. June 2008, 28 (11): 3713–28. PMC 2423283  . PMID 18299392. doi:10.1128/MCB.02263-07. 
  • Morey C, Navarro P, Debrand E, Avner P, Rougeulle C, Clerc P. The region 3' to Xist mediates X chromosome counting and H3 Lys-4 dimethylation within the Xist gene. The EMBO Journal. February 2004, 23 (3): 594–604. PMC 1271805  . PMID 14749728. doi:10.1038/sj.emboj.7600071. 
  • Munroe SH, Lazar MA. . The Journal of Biological Chemistry. 25 November 1991, 266 (33): 22083–6 [2014-02-01]. PMID 1657988. （原始内容存档于2019-07-10）. 
  • Muslimov IA, Banker G, Brosius J, Tiedge H. Activity-dependent regulation of dendritic BC1 RNA in hippocampal neurons in culture. The Journal of Cell Biology. June 1998, 141 (7): 1601–11. PMC 1828539  . PMID 9647652. doi:10.1083/jcb.141.7.1601. 
  • Nesterova TB, Barton SC, Surani MA, Brockdorff N. Loss of Xist imprinting in diploid parthenogenetic preimplantation embryos. Developmental Biology. July 2001, 235 (2): 343–50. PMID 11437441. doi:10.1006/dbio.2001.0295. 
  • Nickerson JA, Krochmalnic G, Wan KM, Penman S. Chromatin architecture and nuclear RNA. Proceedings of the National Academy of Sciences of the United States of America. January 1989, 86 (1): 177–81. Bibcode:1989PNAS...86..177N. PMC 286427  . PMID 2911567. doi:10.1073/pnas.86.1.177. 
  • Ogawa Y, Sun BK, Lee JT. Intersection of the RNA interference and X-inactivation pathways. Science. June 2008, 320 (5881): 1336–41. Bibcode:2008Sci...320.1336O. PMC 2584363  . PMID 18535243. doi:10.1126/science.1157676. 
  • Pagano JM, Farley BM, McCoig LM, Ryder SP. Molecular basis of RNA recognition by the embryonic polarity determinant MEX-5. The Journal of Biological Chemistry. March 2007, 282 (12): 8883–94. PMID 17264081. doi:10.1074/jbc.M700079200. 
  • Pang KC, Frith MC, Mattick JS. Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function. Trends in Genetics. January 2006, 22 (1): 1–5. PMID 16290135. doi:10.1016/j.tig.2005.10.003. 
  • Panganiban G, Rubenstein JL. . Development. 1 October 2002, 129 (19): 4371–86 [2014-02-01]. PMID 12223397. （原始内容存档于2019-07-10）. 
  • Pasmant E, Laurendeau I, Héron D, Vidaud M, Vidaud D, Bièche I. Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Research. April 2007, 67 (8): 3963–9. PMID 17440112. doi:10.1158/0008-5472.CAN-06-2004. 
  • Pauler FM, Koerner MV, Barlow DP. Silencing by imprinted noncoding RNAs: is transcription the answer?. Trends in Genetics. June 2007, 23 (6): 284–92. PMID 17445943. doi:10.1016/j.tig.2007.03.018. 
  • Pennacchio LA, Ahituv N, Moses AM; et al. In vivo enhancer analysis of human conserved non-coding sequences. Nature. November 2006, 444 (7118): 499–502. Bibcode:2006Natur.444..499P. PMID 17086198. doi:10.1038/nature05295. 
  • Perkel, Jeffrey M. Visiting "Noncodarnia". BioTechniques (paper). 2013, 54 (6): 301–304. PMID 23750541. doi:10.2144/000114037. "We're calling long noncoding RNAs a class, when actually the only definition is that they are longer than 200 bp," says Ana Marques, a Research Fellow at the University of Oxford who uses evolutionary approaches to understand lncRNA function. 
  • Pibouin L, Villaudy J, Ferbus D; et al. Cloning of the mRNA of overexpression in colon carcinoma-1: a sequence overexpressed in a subset of colon carcinomas. Cancer Genetics and Cytogenetics. February 2002, 133 (1): 55–60. PMID 11890990. doi:10.1016/S0165-4608(01)00634-3. 
  • Pollard KS, Salama SR, King B; et al. Forces shaping the fastest evolving regions in the human genome. PLoS Genetics. October 2006, 2 (10): e168. PMC 1599772  . PMID 17040131. doi:10.1371/journal.pgen.0020168. 
  • Pollard KS, Salama SR, Lambert N; et al. An RNA gene expressed during cortical development evolved rapidly in humans. Nature. September 2006, 443 (7108): 167–72. Bibcode:2006Natur.443..167P. PMID 16915236. doi:10.1038/nature05113. 
  • Ponjavic J, Ponting CP, Lunter G. Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. Genome Research. May 2007, 17 (5): 556–65. PMC 1855172  . PMID 17387145. doi:10.1101/gr.6036807. 
  • PMID 21047393
  • Reis EM, Nakaya HI, Louro R; et al. Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer. Oncogene. August 2004, 23 (39): 6684–92. PMID 15221013. doi:10.1038/sj.onc.1207880. 
  • Rinn JL, Kertesz M, Wang JK; et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. June 2007, 129 (7): 1311–23. PMC 2084369  . PMID 17604720. doi:10.1016/j.cell.2007.05.022. 
  • Rodríguez-Campos A, Azorín F. RNA is an integral component of chromatin that contributes to its structural organization. PLoS ONE. 2007, 2 (11): e1182. Bibcode:2007PLoSO...2.1182R. PMC 2063516  . PMID 18000552. doi:10.1371/journal.pone.0001182. 
  • Sanchez-Elsner T, Gou D, Kremmer E, Sauer F. Noncoding RNAs of trithorax response elements recruit Drosophila Ash1 to Ultrabithorax. Science. February 2006, 311 (5764): 1118–23. Bibcode:2006Sci...311.1118S. PMID 16497925. doi:10.1126/science.1117705. 
  • Schoeftner S, Blasco MA. Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nature Cell Biology. February 2008, 10 (2): 228–36. PMID 18157120. doi:10.1038/ncb1685. 
  • Shamovsky I, Nudler E. Gene control by large noncoding RNAs. Science's STKE : Signal Transduction Knowledge Environment. October 2006, 2006 (355): pe40. PMID 17018852. doi:10.1126/stke.3552006pe40. 
  • Shamovsky I, Nudler E. Modular RNA heats up. Molecular Cell. February 2008, 29 (4): 415–7. PMID 18313380. doi:10.1016/j.molcel.2008.02.001. 
  • Shirasawa S, Harada H, Furugaki K; et al. SNPs in the promoter of a B cell-specific antisense transcript, SAS-ZFAT, determine susceptibility to autoimmune thyroid disease. Human Molecular Genetics. October 2004, 13 (19): 2221–31. PMID 15294872. doi:10.1093/hmg/ddh245. 
  • Siepel A, Bejerano G, Pedersen JS; et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Research. August 2005, 15 (8): 1034–50. PMC 1182216  . PMID 16024819. doi:10.1101/gr.3715005. 
  • Singh K, Carey M, Saragosti S, Botchan M. Expression of enhanced levels of small RNA polymerase III transcripts encoded by the B2 repeats in simian virus 40-transformed mouse cells. Nature. 1985, 314 (6011): 553–6. Bibcode:1985Natur.314..553S. PMID 2581137. doi:10.1038/314553a0. 
  • Sleutels F, Zwart R, Barlow DP. The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature. February 2002, 415 (6873): 810–3. PMID 11845212. doi:10.1038/415810a. 
  • Smith NG, Brandström M, Ellegren H. Evidence for turnover of functional noncoding DNA in mammalian genome evolution. Genomics. November 2004, 84 (5): 806–13. PMID 15475259. doi:10.1016/j.ygeno.2004.07.012. 
  • Sonkoly E, Bata-Csorgo Z, Pivarcsi A; et al. Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS. The Journal of Biological Chemistry. June 2005, 280 (25): 24159–67. PMID 15855153. doi:10.1074/jbc.M501704200. 
  • Struhl K. Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nature Structural & Molecular Biology. February 2007, 14 (2): 103–5. PMID 17277804. doi:10.1038/nsmb0207-103. 
  • Tang RB, Wang HY, Lu HY; et al. Increased level of polymerase III transcribed Alu RNA in hepatocellular carcinoma tissue. Molecular Carcinogenesis. February 2005, 42 (2): 93–6. PMID 15593371. doi:10.1002/mc.20057. 
  • Tiedge H, Chen W, Brosius J. . Journal of Neuroscience. 1 June 1993, 13 (6): 2382–90 [2014-02-01]. PMID 7684772. （原始内容存档于2019-07-10）. 
  • Tiedge H, Fremeau RT, Weinstock PH, Arancio O, Brosius J. Dendritic location of neural BC1 RNA. Proceedings of the National Academy of Sciences of the United States of America. March 1991, 88 (6): 2093–7. Bibcode:1991PNAS...88.2093T. PMC 51175  . PMID 1706516. doi:10.1073/pnas.88.6.2093. 
  • Torarinsson E, Sawera M, Havgaard JH, Fredholm M, Gorodkin J. Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure. Genome Research. July 2006, 16 (7): 885–9. PMC 1484455  . PMID 16751343. doi:10.1101/gr.5226606. 
  • Torarinsson E, Sawera M, Havgaard JH, Fredholm M, Gorodkin J. Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure. Genome Research. July 2006, 16 (7): 885–9. PMC 1484455  . PMID 16751343. doi:10.1101/gr.5226606. 
  • Tufarelli C, Stanley JA, Garrick D; et al. Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease. Nature Genetics. June 2003, 34 (2): 157–65. PMID 12730694. doi:10.1038/ng1157. 
  • Umlauf D, Goto Y, Cao R; et al. Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes. Nature Genetics. December 2004, 36 (12): 1296–300. PMID 15516932. doi:10.1038/ng1467. 
  • Visel A, Prabhakar S, Akiyama JA; et al. Ultraconservation identifies a small subset of extremely constrained developmental enhancers. Nature Genetics. February 2008, 40 (2): 158–60. PMC 2647775  . PMID 18176564. doi:10.1038/ng.2007.55. 
  • Wang H, Iacoangeli A, Lin D; et al. Dendritic BC1 RNA in translational control mechanisms. The Journal of Cell Biology. December 2005, 171 (5): 811–21. PMC 1828541  . PMID 16330711. doi:10.1083/jcb.200506006. 
  • Wang X, Arai S, Song X; et al. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature. July 2008, 454 (7200): 126–30. Bibcode:2008Natur.454..126W. PMC 2823488  . PMID 18509338. doi:10.1038/nature06992. 
  • Waterston RH, Lindblad-Toh K, Birney E; et al. Initial sequencing and comparative analysis of the mouse genome. Nature. December 2002, 420 (6915): 520–62. Bibcode:2002Natur.420..520W. PMID 12466850. doi:10.1038/nature01262. 
  • Wutz A, Gribnau J. X inactivation Xplained. Current Opinion in Genetics & Development. October 2007, 17 (5): 387–93. PMID 17869504. doi:10.1016/j.gde.2007.08.001. 
  • Wutz A, Rasmussen TP, Jaenisch R. Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nature Genetics. February 2002, 30 (2): 167–74. PMID 11780141. doi:10.1038/ng820. 
  • Yang S, Tutton S, Pierce E, Yoon K. Specific double-stranded RNA interference in undifferentiated mouse embryonic stem cells. Molecular and Cellular Biology. November 2001, 21 (22): 7807–16. PMC 99950  . PMID 11604515. doi:10.1128/MCB.21.22.7807-7816.2001. 
  • Yik JH, Chen R, Nishimura R, Jennings JL, Link AJ, Zhou Q. Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Molecular Cell. October 2003, 12 (4): 971–82. PMID 14580347. doi:10.1016/S1097-2765(03)00388-5. 
  • Yu W, Gius D, Onyango P; et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature. January 2008, 451 (7175): 202–6. Bibcode:2008Natur.451..202Y. PMC 2743558  . PMID 18185590. doi:10.1038/nature06468. 
  • Zearfoss NR, Chan AP, Kloc M, Allen LH, Etkin LD. Identification of new Xlsirt family members in the Xenopus laevis oocyte. Mechanisms of Development. April 2003, 120 (4): 503–9. PMID 12676327. doi:10.1016/S0925-4773(02)00459-8. 
  • Zwart R, Sleutels F, Wutz A, Schinkel AH, Barlow DP. Bidirectional action of the Igf2r imprint control element on upstream and downstream imprinted genes. Genes & Development. September 2001, 15 (18): 2361–6. PMC 312779  . PMID 11562346. doi:10.1101/gad.206201. 

六月 30, 2023
长链非编码核糖核酸, 英語, long, coding, rnas, 简称为lncrna, 指的是长于200核苷酸的不编码蛋白质的转录物, perkel, 2013, 该有些武断的界定将与较小的调控核糖核酸区分开来, 后者如微核糖核酸, mirnas, 小干扰核糖核酸, sirnas, piwi互作核糖核酸类, pirnas, 小核仁核糖核酸, snornas, 及其它短核糖核酸, 2013, 目录, 的丰度, 的基因组组织, 的保守性, 的功能, 长链非编码rna类在基因转录调控中的作用, 长链非编码rna类在基. 长链非编码核糖核酸 英語 long non coding RNAs 简称为lncRNA 指的是长于200核苷酸的不编码蛋白质的转录物 Perkel 2013 该有些武断的界定将长链非编码核糖核酸与较小的调控核糖核酸区分开来 后者如微核糖核酸 miRNAs 小干扰核糖核酸 siRNAs Piwi互作核糖核酸类 piRNAs 小核仁核糖核酸 snoRNAs 及其它短核糖核酸 Ma 2013 目录 1 长链非编码核糖核酸的丰度 2 长链非编码核糖核酸的基因组组织 3 长链非编码核糖核酸的保守性 4 长链非编码核糖核酸的功能 4 1 长链非编码RNA类在基因转录调控中的作用 4 1 1 长链非编码RNA类在基因特异性转录中的作用 4 1 2 长链非编码RNA调控基础转录机器 4 2 长链非编码RNA类在基因转录后调控中的作用 4 2 1 长链非编码RNA类在剪接调控中的作用 4 2 2 长链非编码RNA类在翻译调控中的作用 4 2 3 长链非编码RNA类在siRNA导向的基因调控中的作用 4 3 长链非编码RNA类在表观遗传调控中的作用 4 3 1 基因印记 4 3 2 Xist与X 染色体失活 4 3 3 端粒非编码RNA类 5 长链非编码RNA类在衰老与疾病中的作用 6 外部链接 7 另见 8 参考文献长链非编码核糖核酸的丰度 编辑近年研究显示人类基因组中的转录只有五分之一与蛋白编码基因有关 Kapranov 2007 这说明至少有较编码核糖核酸序列四倍多的长链非编码核糖核酸 而像FANTOM 哺乳动物cDNA功能注释 等的大规模互补脱氧核糖核酸 cDNA 测序计划揭示了转录的复杂性 Carninci 2005 FANTOM3计划从约一万个不同的基因座中鉴定出了约三万五千条非编码转录物它们有着与mRNA类类似的特征 包括5 端有帽 受到剪接及多聚腺苷酸化 但只有很小的開放閱讀框 ORF 或根本没有 Carninci 2005 然而长链非编码RNA的丰度是意料之外的 其数目代表的是保守估计的最低值 因为这种方法忽略了许多单独的转录物及非多腺苷酸化的转录物 瓦片阵列数据显示出40 以上的转录物是非多腺苷酸化的 Cheng 2005 尽管如此 在这些cDNA文库中明确鉴定非编码RNA类仍是充满挑战的 因为该方法无法区分非编码转录物及蛋白编码转录物 长链非编码核糖核酸的基因组组织 编辑目前将哺乳动物基因组的全景描绘为 长段的基因间空间将多个转录 焦点 分割开 Carninci 2005 然而长链非编码核糖核酸正位于这些基因间区段中并由此转录出来 其中大多数是与其它转录物之间呈错综复杂的正义或反义重叠 这些转录物往往包括了蛋白编码基因 Kapranov 2007 在正义或反义链上的多个不同的编码或非编码转录物共享这些转录焦点中的基因组序列 Birney 2007 使得这些重叠的亚型之间产生复杂的层次结构 例如 8961个cDNA中的3012个曾被FANTOM2计划注释为编码序列中的一段截短序列 但后来又重新被指定为蛋白编码cDNA中的新非编码RNA变异体 Carninci 2005 尽管编码RNA及非编码RNA的交错排列具备一定的丰度和保守性 并可能意味着它们两者之间具有某些生物学关联性 但仍无法对这些复杂的焦点结构进行简单的评价 GENCODE共同体已综合性整理及分析了一些人类长链非编码RNA的注释及它们的基因组结构 修饰 细胞定位及组织表达谱 Derrien 2012 他们的分析结果说明人类长链非编码RNA易形成具有两个外显子的转录物 Derrien 2012 长链非编码核糖核酸的保守性 编辑如微核糖核酸及小核仁核糖核酸等的众多小型核糖核酸都显现出了跨多物种的保守性 Bentwich 2005 与之相反 大多数长链非编码核糖核酸则保守性不强 这一点常被引用为其不具备功能的证据 Brosius 2005 Struhl 2007 然而 如Air及Xist等经过详细研究的长链非编码RNA 它们的保守性也很差 Nesterova 2001 这意味着非编码RNA类可能受到不同的选择压力 Pang 2006 mRNA必须保守密码子的正常用法并防止单个长ORF中出现移码突变 然而对长链非编码RNA的选择压力可能只会令其保守其中的较短区域 这些较短区域对于结构或序列特异性相互作用较为关键 因此 我们可见选择压力只会作用于长链非编码RNA转录物的小块区域 仍然要看到 尽管长链非编码RNA总体来说保守性较低 但仍可见许多长链非编码RNA具有较强的保守元件 例如 高度保守的phastCons元件中有19 存在于已知的内含子中 而其它32 存在于未注释的区域之中 Siepel 2005 此外 人类长链非编码RNA中的具有代表性的一类长链非编码RNA在碱基取代和插入 缺失速率方面显现出较小但显著的降低 这一现象指示了净化选择压力使得转录物的完整性得到保守 这在序列 启动子及剪接三种水平上体现出来 Ponjavic 2007 非编码核糖核酸的保守性差可能是近期且快速的适应性选择的结果 例如 非编码核糖核酸较蛋白编码基因可能对进化压力可塑性更强 如Xist或Air等的许多世系特异性非编码RNA的存在可以证明这一点 Pang 2006 相对于黑猩猩基因组来说人类基因组中经受近期进化改变的保守区域确实主要存在于非编码区域 其中很多已有详尽描述 Pollard 2006 Pollard 2006 其中包括一条名为HAR1F的非编码RNA 该基因在人类中经历了快速的进化变化 且特异性地在人类新皮质的卡哈尔 雷济厄斯氏细胞中特异性表达 Pollard 2006 现有报道称许多功能已确定的RNA进化速率也很快 Pang 2006 Smith 2004 这可能由于这些序列受到结构 功能约束时表现得更灵活 我们可以期待在这些序列中发现新的进化方式 人类基因组中有数千条序列的一级序列保守性较差 但有证据显示它们RNA二級結構却存在着保守性 Torarinsson 2006 Torarinsson 2008 这支持了上述论点 长链非编码核糖核酸的功能 编辑cDNA文库的大规模测序及更先进的基于下一代测序的转录组测序表明哺乳动物中长链非编码核糖核酸的数量大约是几万条 然而 虽然越来越多的证据提示大多数长链非编码核糖核酸具有功能 Mercer 2009 Dinger 2009 但相对只有一小部分已被证明有生物学重大意义 截至2012年十二月 约有127条长链非编码RNA在LncRNAdb 一个描述长链非编码RNA的文献数据库 中有功能注释 Amral 2011 长链非编码RNA类在基因转录调控中的作用 编辑 长链非编码RNA类在基因特异性转录中的作用 编辑 RNA转录在真核生物中是一个受到严密调控的过程 非编码RNA可以靶向该进程的多个方面 包括靶向转录激活因子或转录抑制因子 如RNA聚合酶 RNAP 等转录反应中的各组分 甚至是DNA双螺旋结构 以达到调控基因转录及表达的目的 Goodrich 2006 非编码RNA将这些机制结合在一起可以组成为一个包括转录因子在内的调控网络 可以精细地调控复杂真核生物的基因表达 非编码RNA通过多种不同的机制调节转录因子的功能 包括充当共调控因子的角色 修饰转录因子的活性或是调控共调控因子的活性 例如 非编码RNA Evf 2作为同源异形框转录因子Dlx2的共激活因子 Dlx2在前脑发育及神经发生中起到重要作用 Feng 2006 Panganiban 2002 Evf 2转录自位于Dlx5与Dlx6基因之间的超保守元件 音猬因子在前脑发育过程中诱导该长链的转录 Feng 2006 Evf 2接着将Dlx2转录因子招募到同一个超保守元件处 Dlx2在此处诱导Dlx5的表达 哺乳动物基因组中存在其它一些可转录且执行增强子功能的超级保守或高度保守元件 这提示Evf 2可作为范例阐述脊椎动物生长过程中以复杂表达的形式严密调控重要发育基因的普遍机制 Pennacchio 2006 Visel 2008 近期研究也确实发现与之类似的其它非编码超保守元件的转录及表达在人类白血病中出现异常 且促进结肠癌细胞的凋亡 这提示了它们涉及到肿瘤形成 Calin 2007 局部的非编码RNA类可以招募转录机制对附近蛋白编码基因的转录加以调控 TLS 英語 translocated in liposarcoma 是一种结合RNA的蛋白 它结合到CREB结合蛋白和组蛋白乙酰基转移酶p300上并抑制这两者在靶基因周期蛋白D1上的活性 从而起到抑制后者的作用 作为DNA受损信号的响应 长链非编码RNA以低水平表达出来并拴在周期蛋白D1基因的5 调控区域上 这指导了TLS招募到周期蛋白D1启动子上 Wang 2008 除此之外 这些局部的非编码RNA作为配体调控TLS的活性 从更广泛的层面上说 这一机制使得细胞可以利用RNA结合蛋白 它们组成了哺乳动物蛋白质组中的最庞大的种类之一 并在转录程序控制中整合它们的功能 在X染色体失活的情况下一些基因仍可以转录 近期对逃避染色体失活控制的染色体区域进行研究 发现其中表达的长链非编码RNA可能介导了这一过程 Reinius 2010 长链非编码RNA调控基础转录机器 编辑 非编码RNA还可以靶向通用转录因子 后者是RNAP 转录所有基因所必需的 Goodrich 2006 这些通用因子包括了起始复合体中组装在启动子上或涉及转录延伸的部件 转录自二氢叶酸还原酶 DHFR 基因上游次要启动子的一条非编码RNA进入DHFR主要启动子 形成稳定的RNA DNA三股螺旋以阻止转录辅因子TF B结合到其上 Martianov 2007 已知真核染色体上存在着数千个三股螺旋 Lee 1987 这一调控基因表达的新机制可能事实上代表这些三股螺旋在控制启动子上起到的广泛作用 U1非编码RNA通过结合到TF H上并刺激其对RNAP 的C 端以实现诱导转录起始 Kwek 2002 相反 非编码RNA 7SK可通过下列方式起到抑制转录延伸的作用 7SK首先与HEXIM1 2结合 形成抑制性复合物 该复合物阻止PTEFb通用转录因子去磷酸化RNAP 的C 端结构域 Kwek 2002 Yang 2001 Yik 2003 当细胞处于应激状况下可以抑制全局延伸 这些例子中的机制可以绕开单个启动子上特异性的调控模式 介导起始及延伸转录机器工作水平发生直接改变 提供了迅速影响基因表达全局改变的方法 现也证明非编码重复序列有着介导全局调控的能力 人类的短散在核内 SINE Alu元件及小鼠中同源的B1和B2元件是基因组中丰度最高的可移动性元件 分别组成了人类和小鼠基因组的约10 和约6 Lander 2001 Waterston 2002 在如热休克等环境应激情况下这些元件被RNAP 转录为非编码RNA Liu 1995 后者接下来会以高亲和度的方式与RNAP 结合并阻止其形成为有活性的前起始复合物 Allen 2004 Espinoza 2004 Espinoza 2007 Mariner amp Walters 2008 这使得在响应应激的情况下可以大范围并迅速抑制基因的表达 Allen 2004 Mariner amp Walters 2008 对Alu元件的RNA转录物中的功能序列进行分析后 发现其亦有类似于蛋白质转录因子中结构域的模块化结构 Shamovsky 2008 Alu元件RNA包括两个 臂 每个臂都可以结合到一个RNAP 分子上 体外实验表明该RNA还具有两个调控结构域 起到抑制RNAP 转录活性的作用 Mariner 2008 These two loosely structured domains may even be concatenated to other ncRNAs such as B1 elements to impart their repressive role Mariner amp Walters 2008 The abundance and distribution of Alu elements and similar repetitive elements throughout the mammalian genome may be partly due to these functional domains being co opted into other long ncRNAs during evolution with the presence of functional repeat sequence domains being a common characteristic of several known long ncRNAs including Kcnq1ot1 Xlsirt and Xist Mattick 2003 Mohammad 2008 Wutz 2002 Zearfoss 2003 除了热休克外 如病毒感染 the expression of SINE elements including Alu B1 and B2 RNAs increases during cellular stress such as viral infection Singh 1985 in some cancer cells Tang 2005 where they may similarly regulate global changes to gene expression The ability of Alu and B2 RNA to bind directly to RNAP II provides a broad mechanism to repress transcription Espinoza 2004 Mariner amp Walters 2008 Nevertheless there are specific exceptions to this global response where Alu or B2 RNAs are not found at activated promoters of genes undergoing induction such as the heat shock genes Mariner amp Walters 2008 This additional hierarchy of regulation that exempts individual genes from the generalised repression also involves a long ncRNA heat shock RNA 1 HSR 1 It was argued that HSR 1 is present in all cells in an inactive state but upon stress is activated to induce the expression of heat shock genes Shamovsky 2006 The authors found that this activation involves a conformational alteration to the structure of HSR 1 in response to rising temperatures thereby permitting its interaction with the transcriptional activator HSF 1 that subsequently undergoes trimerisation and induces the expression of heat shock genes Shamovsky 2006 In the broad sense these examples illustrate a regulatory circuit nested witin ncRNAs whereby Alu or B2 RNAs repress general gene expression while other ncRNAs activate the expression of specific genes 长链非编码RNA类在基因转录后调控中的作用 编辑 除了在转录水平上调控 ncRNAs 也在转录后水平调控mRNA加工的不同方面 与小调控RNAs 例如微小RNAs和小核仁RNAs 类似 ncRNAs 的功能包括与目标mRNA进行互补碱基配对 互补ncRNA和mRNA形成的RNA双链可能为需要结合反式作用因子的mRNA募集关键因子 可能影响转录后水平基因表达的每一步 包括前体mRNA加工 剪接 运输 翻译以及降解 长链非编码RNA类在剪接调控中的作用 编辑 The splicing of mRNA can induce its translation and functionally diversify the repertoire of proteins it encodes The Zeb2 mRNA which has a particularly long 5 UTR requires the retention of a 5 UTR intron that contains an internal ribosome entry site for efficient translation Beltran 2008 However retention of the intron is dependent on the expression of an antisense transcript that complements the intronic 5 splice site Beltran 2008 Therefore the ectopic expression of the antisense transcript represses splicing and induces translation of the Zeb2 mRNA during mesenchymal development Likewise the expression of an overlapping antisense Rev ErbAa2 transcript controls the alternative splicing of the thyroid hormone receptor ErbAa2 mRNA to form two antagonistic isoforms Munroe 1991 长链非编码RNA类在翻译调控中的作用 编辑 NcRNA may also apply additional regulatory pressures during translation a property particularly exploited in neurons where the dendritic or axonal translation of mRNA in response to synaptic activity contributes to changes in synaptic plasticity and the remodelling of neuronal networks The RNAP III transcribed BC1 and BC200 ncRNAs that previously derived from tRNAs are expressed in the mouse and human central nervous system respectively Tiedge 1993 Tiedge 1991 BC1 expression is induced in response to synaptic activity and synaptogenesis and is specifically targeted to dendrites in neurons Muslimov 1998 Sequence complementarity between BC1 and regions of various neuron specific mRNAs also suggest a role for BC1 in targeted translational repression Wang 2005 Indeed it was recently shown that BC1 is associated with translational repression in dendrites to control the efficiency of dopamine D2 receptor mediated transmission in the striatum Centonze 2007 and BC1 RNA deleted mice exhibit behavioural changes with reduced exploration and increased anxiety Lewejohann 2004 长链非编码RNA类在siRNA导向的基因调控中的作用 编辑 In addition to masking key elements within single stranded RNA the formation of double stranded RNA duplexes can also provide a substrate for the generation of endogenous siRNAs endo siRNAs in Drosophila and mouse oocytes Golden 2008 The annealing of complementary sequences such as antisense or repetitive regions between transcripts forms an RNA duplex that may be processed by Dicer 2 into endo siRNAs Also long ncRNAs that form extended intramolecular hairpins may be processed into siRNAs compellingly illustrated by the esi 1 and esi 2 transcripts Czech 2008 Endo siRNAs generated from these transcripts seem particularly useful in suppressing the spread of mobile transposon elements within the genome in the germline However the generation of endo siRNAs from antisense transcripts or pseudogenes may also silence the expression of their functional counterparts via RISC effector complexes acting as an important node that integrates various modes of long and short RNA regulation as exemplified by the Xist and Tsix see above Ogawa 2008 长链非编码RNA类在表观遗传调控中的作用 编辑 包括组蛋白和DNA甲基化 组蛋白乙酰化和SUMO化等在内的表观遗传修饰影响了染色体生物学的众多方面 主要包括通过对广大染色质区域进行重塑从而调控大量基因 Kiefer 2007 Mikkelsen 2007 一段时间以来 RNA作为染色质的有机组成部分已被人知晓 Nickerson 1989 Rodriguez Campos 2007 但现在我们才开始认识到RNA在涉及到染色质修饰通路上的意义 Chen 2008 Rinn 2007 Sanchez Elsner 2006 果蝇属中的长链非编码RNA类通过将三胸蛋白Ash1募集到同源异形调控元件并指导其发挥染色质修饰作用的方式诱导同源异形基因Ubx的表达 Sanchez Elsner 2006 后来发现哺乳动物中也存在着相似的调控模式 认为强大的表观遗传机制奠定了胚胎同源异形基因家族的表达谱 而同源异形基因家族是贯穿整个人体发育过程中持续发挥作用的重要因子 Mazo 2007 Rinn 2007 人类同源异形基因家族确实与数百个非编码RNA之间有着相关性 这些非编码RNA在人体发育的时空轴上按顺序表达 这些非编码RNA也定义染色质各区域中组蛋白甲基化程度的差异以及RNA聚合酶可进入染色质的程度 Rinn 2007 其中一条名为HOTAIR的转录自HOXC基因座的非编码RNA通过改变组蛋白三甲基化状态从而使HOXD基因座中长约40kb的区域发生转录沉默 目前认为HOTAIR执行的作用机制是 多梳染色质重塑复合物具有操纵细胞表观遗传状态的功能 而HOTAIR以反式调控的方式指导该功能的发挥并继而影响基因的表达 多梳复合物中的成员包括SUZ12 EZH2和EED等 它们具有RNA结合结构域并可能结合HOTAIR及其它类似的非编码RNA类 Denisenko 1998 Katayama 2005 该例子极好地描绘出了这样一个更广泛的主题 非编码RNA类招募一系列染色质修饰蛋白到特定基因组基因座上并发挥功能 这更加突出了目前所绘制基因组图谱的复杂性 Mikkelsen 2007 发育时期中调控基因表达的染色质修饰有着区域化的模式 大量长链非编码与蛋白编码基因的联系确实帮助塑造了这种模式 例如 大多数蛋白编码基因都具有配对的反义基因 许多抑癌基因在癌症中常受到沉默 一些反义基因使用表观遗传机制使这些抑癌基因沉默 Yu 2008 近期研究发现 在白血病中p15基因和一条反义非编码RNA的表达此消彼长 Yu 2008 经过详细分析发现 p15的反义非编码RNA CDKN2BAS 可通过一种未知机制诱导p15的异染色质和DNA甲基化状态发生改变 因而调控了p15基因的表达 Yu 2008 因此 相关的反义非编码RNA类表达发生异常可能继而沉默了抑癌基因 从而走向癌症发生 基因印记 编辑 最近非编码RNA指导的染色质修饰主题最初是从基因组印记的现象中引出的 基因组印记是仅从母系或父系染色体两者中的一个表达出等位基因的现象 一般来说 印记基因是呈簇状排列于染色体上 这提示 印记的机制是作用于局部的染色质区域上而不是针对单个基因 这些基因簇常常与长链非编码RNA相关 长链非编码RNA的表达量与在相同等位上相连锁的蛋白编码基因受到抑制的程度呈正相关 Pauler 2007 详细分析确实显示出非编码RNA Kcnqot1和Igf2r Air在指导基因印记上发挥着重要作用 Braidotti 2004 几乎所有位于Kcnq1基因座Almost all the genes at the Kcnq1 loci are maternally inherited except the paternally expressed antisense ncRNA Kcnqot1 Mitsuya 1999 Transgenic mice with truncated Kcnq1ot fail to silence the adjacent genes suggesting that Kcnqot1 is crucial to the imprinting of genes on the paternal chromosome Mancini Dinardo 2006 It appears that Kcnqot1 is able to direct the trimethylation of lysine 9 H3K9me3 and 27 of histone 3 H3K27me3 to an imprinting centre that overlaps the Kcnqot1 promoter and actually resides within a Kcnq1 sense exon Umlauf 2004 Similar to HOTAIR see above Eed Ezh2 Polycomb complexes are recruited to the Kcnq1 loci paternal chromosome possibly by Kcnqot1 where they may mediate gene silencing through repressive histone methylation Umlauf 2004 A differentially methylated imprinting centre also overlaps the promoter of a long antisense ncRNA Air that is responsible for the silencing of neighbouring genes at the Igf2r locus on the paternal chromosome Sleutels 2002 Zwart 2001 The presence of allele specific histone methylation at the Igf2r locus suggests Air also mediates silencing via chromatin modification Fournier 2002 Xist与X 染色体失活 编辑 The inactivation of a X chromosome in female placental mammals is directed by one of the earliest and best characterized long ncRNAs Xist Wutz 2007 The expression of Xist from the future inactive X chromosome and its subsequent coating of the inactive X chromosome occurs during early embryonic stem cell differentiation Xist expression is followed by irreversible layers of chromatin modifications that include the loss of the histone H3K9 acetylation and H3K4 methylation that are associated with active chromatin and the induction of repressive chromatin modifications including H4 hypoacetylation H3K27 trimethylation Wutz 2007 H3K9 hypermethylation and H4K20 monomethylation as well as H2AK119 monoubiquitylation These modifications coincide with the transcriptional silencing of the X linked genes Morey 2004 Xist RNA also localises the histone variant macroH2A to the inactive X chromosome Costanzi 1998 There are additional ncRNAs that are also present at the Xist loci including an antisense transcript Tsix which is expressed from the future active chromosome and able to repress Xist expression by the generation of endogenous siRNA Ogawa 2008 Together these ncRNAs ensure that only one X chromosome is active in female mammals 端粒非编码RNA类 编辑 Telomeres form the terminal region of mammalian chromosomes and are essential for stability and aging and play central roles in diseases such as cancer Blasco 2007 Telomeres have been long considered transcriptionally inert DNA protein complexes until it was recently shown that telomeric repeats may be transcribed as telomeric RNAs TelRNAs Schoeftner 2008 or telomeric repeat containing RNAs Azzalin 2007 These ncRNAs are heterogeneous in length transcribed from several sub telomeric loci and physically localise to telomeres Their association with chromatin which suggests an involvement in regulating telomere specific heterochromatin modifications is repressed by SMG proteins that protect chromosome ends from telomere loss Azzalin 2007 In addition TelRNAs block telomerase activity in vitro and may therefore regulate telomerase activity Schoeftner 2008 Although early these studies suggest an involvement for telomeric ncRNAs in various aspects of telomere biology 长链非编码RNA类在衰老与疾病中的作用 编辑外部链接 编辑LncRNAWiki 页面存档备份 存于互联网档案馆 a wiki based database for management of human lncRNAs ChIPBase database 永久失效連結 decodes the transcriptional regulation of lncRNAs from ChIP Seq and provides expression profiles of lncRNAs lincRNAs from RNA Seq data across 22 tissues lncRNAdb database 页面存档备份 存于互联网档案馆 providing comprehensive annotations of functional long non coding RNAs lncRNAs Long RNA Synthesis 页面存档备份 存于互联网档案馆 chemical long RNA synthesis and long RNA synthesis by transcription 另见 编辑参考文献 编辑Allen E Xie Z Gustafson AM Sung GH Spatafora JW Carrington JC Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana Nature Genetics December 2004 36 12 1282 90 PMID 15565108 doi 10 1038 ng1478 PMID 21112873 Azzalin CM Reichenbach P Khoriauli L Giulotto E Lingner J Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends Science November 2007 318 5851 798 801 Bibcode 2007Sci 318 798A PMID 17916692 doi 10 1126 science 1147182 Beltran M Puig I Pena C et al A natural antisense transcript regulates Zeb2 Sip1 gene expression during Snail1 induced epithelial mesenchymal transition Genes amp Development March 2008 22 6 756 69 PMC 2275429 PMID 18347095 doi 10 1101 gad 455708 引文格式1维护 显式使用等标签 link Bentwich I Avniel A Karov Y et al Identification of hundreds of conserved and nonconserved human microRNAs Nature Genetics July 2005 37 7 766 70 PMID 15965474 doi 10 1038 ng1590 引文格式1维护 显式使用等标签 link Birney E Stamatoyannopoulos JA Dutta A et al Identification and analysis of functional elements in 1 of the human genome by the ENCODE pilot project Nature June 2007 447 7146 799 816 Bibcode 2007Natur 447 799B PMC 2212820 PMID 17571346 doi 10 1038 nature05874 引文格式1维护 显式使用等标签 link Blasco MA Telomere length stem cells and aging Nature Chemical Biology October 2007 3 10 640 9 PMID 17876321 doi 10 1038 nchembio 2007 38 Braidotti G Baubec T Pauler F et al The Air noncoding RNA an imprinted cis silencing transcript Cold Spring Harbor Symposia on Quantitative Biology 2004 69 55 66 PMID 16117633 doi 10 1101 sqb 2004 69 55 引文格式1维护 显式使用等标签 link Broadbent HM Peden JF Lorkowski S et al Susceptibility to coronary artery disease and diabetes is encoded by distinct tightly linked SNPs in the ANRIL locus on chromosome 9p Human Molecular Genetics 2008 17 6 806 14 PMID 18048406 doi 10 1093 hmg ddm352 引文格式1维护 显式使用等标签 link Brosius J Waste not want not transcript excess in multicellular eukaryotes Trends in Genetics May 2005 21 5 287 8 PMID 15851065 doi 10 1016 j tig 2005 02 014 Calin GA Liu CG Ferracin M et al Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas Cancer Cell September 2007 12 3 215 29 PMID 17785203 doi 10 1016 j ccr 2007 07 027 引文格式1维护 显式使用等标签 link Carninci P Kasukawa T Katayama S et al The transcriptional landscape of the mammalian genome Science September 2005 309 5740 1559 63 Bibcode 2005Sci 309 1559F PMID 16141072 doi 10 1126 science 1112014 引文格式1维护 显式使用等标签 link Centonze D Rossi S Napoli I et al The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor mediated transmission in the striatum The Journal of Neuroscience August 2007 27 33 8885 92 PMID 17699670 doi 10 1523 JNEUROSCI 0548 07 2007 引文格式1维护 显式使用等标签 link Chen X Xu H Yuan P et al Integration of external signaling pathways with the core transcriptional network in embryonic stem cells Cell June 2008 133 6 1106 17 PMID 18555785 doi 10 1016 j cell 2008 04 043 引文格式1维护 显式使用等标签 link Cheng J Kapranov P Drenkow J et al Transcriptional maps of 10 human chromosomes at 5 nucleotide resolution Science May 2005 308 5725 1149 54 Bibcode 2005Sci 308 1149C PMID 15790807 doi 10 1126 science 1108625 引文格式1维护 显式使用等标签 link Costanzi C Pehrson JR Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals Nature June 1998 393 6685 599 601 Bibcode 1998Natur 393 599C PMID 9634239 doi 10 1038 31275 Czech B Malone CD Zhou R et al An endogenous small interfering RNA pathway in Drosophila Nature June 2008 453 7196 798 802 Bibcode 2008Natur 453 798C PMID 18463631 doi 10 1038 nature07007 引文格式1维护 显式使用等标签 link Denisenko O Shnyreva M Suzuki H Bomsztyk K Point mutations in the WD40 domain of Eed block its interaction with Ezh2 Molecular and Cellular Biology 1 October 1998 18 10 5634 42 2014 02 01 PMC 109149 PMID 9742080 原始内容存档于2019 07 10 PMID 22955988 Dieci G Fiorino G Castelnuovo M Teichmann M Pagano A The expanding RNA polymerase III transcriptome Trends in Genetics December 2007 23 12 614 22 PMID 17977614 doi 10 1016 j tig 2007 09 001 PMID 19770204 Eis PS Tam W Sun L et al Accumulation of miR 155 and BIC RNA in human B cell lymphomas Proceedings of the National Academy of Sciences of the United States of America March 2005 102 10 3627 32 Bibcode 2005PNAS 102 3627E PMC 552785 PMID 15738415 doi 10 1073 pnas 0500613102 引文格式1维护 显式使用等标签 link Espinoza CA Allen TA Hieb AR Kugel JF Goodrich JA B2 RNA binds directly to RNA polymerase II to repress transcript synthesis Nature Structural amp Molecular Biology September 2004 11 9 822 9 PMID 15300239 doi 10 1038 nsmb812 Espinoza CA Goodrich JA Kugel JF Characterization of the structure function and mechanism of B2 RNA an ncRNA repressor of RNA polymerase II transcription RNA April 2007 13 4 583 96 PMC 1831867 PMID 17307818 doi 10 1261 rna 310307 Faghihi MA Modarresi F Khalil AM et al Expression of a noncoding RNA is elevated in Alzheimer s disease and drives rapid feed forward regulation of beta secretase Nature Medicine July 2008 14 7 723 30 PMC 2826895 PMID 18587408 doi 10 1038 nm1784 引文格式1维护 显式使用等标签 link Feng J Bi C Clark BS Mady R Shah P Kohtz JD The Evf 2 noncoding RNA is transcribed from the Dlx 5 6 ultraconserved region and functions as a Dlx 2 transcriptional coactivator Genes amp Development June 2006 20 11 1470 84 PMC 1475760 PMID 16705037 doi 10 1101 gad 1416106 Fournier C Goto Y Ballestar E et al Allele specific histone lysine methylation marks regulatory regions at imprinted mouse genes The EMBO Journal December 2002 21 23 6560 70 PMC 136958 PMID 12456662 doi 10 1093 emboj cdf655 引文格式1维护 显式使用等标签 link Fu X Ravindranath L Tran N Petrovics G Srivastava S Regulation of apoptosis by a prostate specific and prostate cancer associated noncoding gene PCGEM1 DNA and Cell Biology March 2006 25 3 135 41 PMID 16569192 doi 10 1089 dna 2006 25 135 Golden DE Gerbasi VR Sontheimer EJ An inside job for siRNAs Molecular Cell August 2008 31 3 309 12 PMC 2675693 PMID 18691963 doi 10 1016 j molcel 2008 07 008 Goodrich JA Kugel JF Non coding RNA regulators of RNA polymerase II transcription Nature Reviews Molecular Cell Biology August 2006 7 8 612 6 PMID 16723972 doi 10 1038 nrm1946 Hesman Saey Tina Missing Lincs Science News 17 December 2011 180 13 22 25 2014 02 01 原始内容存档于2013 07 27 Ishii N Ozaki K Sato H et al Identification of a novel non coding RNA MIAT that confers risk of myocardial infarction Journal of Human Genetics 2006 51 12 1087 99 PMID 17066261 doi 10 1007 s10038 006 0070 9 引文格式1维护 显式使用等标签 link Jarinova O Stewart AF Roberts R et al Functional analysis of the chromosome 9p21 3 coronary artery disease risk locus Arteriosclerosis Thrombosis and Vascular Biology October 2009 29 10 1671 77 PMID 19592466 doi 10 1161 ATVBAHA 109 189522 引文格式1维护 显式使用等标签 link Kapranov P Cheng J Dike S et al RNA maps reveal new RNA classes and a possible function for pervasive transcription Science June 2007 316 5830 1484 8 Bibcode 2007Sci 316 1484K PMID 17510325 doi 10 1126 science 1138341 引文格式1维护 显式使用等标签 link Kapranov P Willingham AT Gingeras TR Genome wide transcription and the implications for genomic organization Nature Reviews Genetics June 2007 8 6 413 23 PMID 17486121 doi 10 1038 nrg2083 Kapranov P St Laurent G Raz T et al The majority of total nuclear encoded non ribosomal RNA in a human cell is dark matter un annotated RNA BMC Biol 2010 8 149 2014 02 01 PMC 3022773 PMID 21176148 doi 10 1186 1741 7007 8 149 原始内容存档于2015 11 02 引文格式1维护 显式使用等标签 link Erratum in BMC Biol 2011 9 86 Katayama S Tomaru Y Kasukawa T et al Antisense transcription in the mammalian transcriptome Science September 2005 309 5740 1564 6 Bibcode 2005Sci 309 1564R PMID 16141073 doi 10 1126 science 1112009 引文格式1维护 显式使用等标签 link Kiefer JC Epigenetics in development Developmental Dynamics April 2007 236 4 1144 56 PMID 17304537 doi 10 1002 dvdy 21094 Kim Evidence for bacterial origin of heat shock RNA 1 RNA February 2010 16 2 274 279 PMC 2811656 PMID 20040589 doi 10 1261 rna 1879610 Kwek KY Murphy S Furger A et al U1 snRNA associates with TFIIH and regulates transcriptional initiation Nature Structural Biology November 2002 9 11 800 5 PMID 12389039 doi 10 1038 nsb862 引文格式1维护 显式使用等标签 link Lander ES Linton LM Birren B et al Initial sequencing and analysis of the human genome Nature February 2001 409 6822 860 921 PMID 11237011 doi 10 1038 35057062 引文格式1维护 显式使用等标签 link Lee JS Burkholder GD Latimer LJ Haug BL Braun RP A monoclonal antibody to triplex DNA binds to eucaryotic chromosomes Nucleic Acids Research February 1987 15 3 1047 61 PMC 340507 PMID 2434928 doi 10 1093 nar 15 3 1047 Lewejohann L Skryabin BV Sachser N et al Role of a neuronal small non messenger RNA behavioural alterations in BC1 RNA deleted mice Behavioural Brain Research September 2004 154 1 273 89 PMID 15302134 doi 10 1016 j bbr 2004 02 015 引文格式1维护 显式使用等标签 link Li J Witte DP Van Dyke T Askew DS Expression of the putative proto oncogene His 1 in normal and neoplastic tissues The American Journal of Pathology April 1997 150 4 1297 305 PMC 1858164 PMID 9094986 Lin R Maeda S Liu C Karin M Edgington TS A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas Oncogene February 2007 26 6 851 8 PMID 16878148 doi 10 1038 sj onc 1209846 lincRNA homepage of the Rinn Lab 页面存档备份 存于互联网档案馆 Liu WM Chu WM Choudary PV Schmid CW Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts Nucleic Acids Research May 1995 23 10 1758 65 PMC 306933 PMID 7784180 doi 10 1093 nar 23 10 1758 Liu Y Sanoff HK Cho H et al INK4 ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis PloS One April 2009 4 4 e5027 Bibcode 2009PLoSO 4 5027L PMC 2660422 PMID 19343170 doi 10 1371 journal pone 0005027 引文格式1维护 显式使用等标签 link Mancini Dinardo D Steele SJ Levorse JM Ingram RS Tilghman SM Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes Genes amp Development May 2006 20 10 1268 82 PMC 1472902 PMID 16702402 doi 10 1101 gad 1416906 Mariner PD Walters RD Espinoza CA et al Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock Molecular Cell February 2008 29 4 499 509 PMID 18313387 doi 10 1016 j molcel 2007 12 013 引文格式1维护 显式使用等标签 link Martianov I Ramadass A Serra Barros A Chow N Akoulitchev A Repression of the human dihydrofolate reductase gene by a non coding interfering transcript Nature February 2007 445 7128 666 70 PMID 17237763 doi 10 1038 nature05519 Mattick JS Challenging the dogma the hidden layer of non protein coding RNAs in complex organisms BioEssays October 2003 25 10 930 9 PMID 14505360 doi 10 1002 bies 10332 Mazo A Hodgson JW Petruk S Sedkov Y Brock HW Transcriptional interference an unexpected layer of complexity in gene regulation Journal of Cell Science August 2007 120 Pt 16 2755 61 PMID 17690303 doi 10 1242 jcs 007633 McPherson R Pertsemlidis A Kavaslar N et al A Common Allele on Chromosome 9 Associated with Coronary Heart Disease Science May 2007 316 5830 1488 91 Bibcode 2007Sci 316 1488M PMC 2711874 PMID 17478681 doi 10 1126 science 1142447 引文格式1维护 显式使用等标签 link PMID 19188922 Mikkelsen TS Ku M Jaffe DB et al Genome wide maps of chromatin state in pluripotent and lineage committed cells Nature August 2007 448 7153 553 60 Bibcode 2007Natur 448 553M PMC 2921165 PMID 17603471 doi 10 1038 nature06008 引文格式1维护 显式使用等标签 link Mitsuya K Meguro M Lee MP et al LIT1 an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids Human Molecular Genetics July 1999 8 7 1209 17 PMID 10369866 doi 10 1093 hmg 8 7 1209 引文格式1维护 显式使用等标签 link Mohammad F Pandey RR Nagano T et al Kcnq1ot1 Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region Molecular and Cellular Biology June 2008 28 11 3713 28 PMC 2423283 PMID 18299392 doi 10 1128 MCB 02263 07 引文格式1维护 显式使用等标签 link Morey C Navarro P Debrand E Avner P Rougeulle C Clerc P The region 3 to Xist mediates X chromosome counting and H3 Lys 4 dimethylation within the Xist gene The EMBO Journal February 2004 23 3 594 604 PMC 1271805 PMID 14749728 doi 10 1038 sj emboj 7600071 Munroe SH Lazar MA Inhibition of c erbA mRNA splicing by a naturally occurring antisense RNA The Journal of Biological Chemistry 25 November 1991 266 33 22083 6 2014 02 01 PMID 1657988 原始内容存档于2019 07 10 Muslimov IA Banker G Brosius J Tiedge H Activity dependent regulation of dendritic BC1 RNA in hippocampal neurons in culture The Journal of Cell Biology June 1998 141 7 1601 11 PMC 1828539 PMID 9647652 doi 10 1083 jcb 141 7 1601 Nesterova TB Barton SC Surani MA Brockdorff N Loss of Xist imprinting in diploid parthenogenetic preimplantation embryos Developmental Biology July 2001 235 2 343 50 PMID 11437441 doi 10 1006 dbio 2001 0295 Nickerson JA Krochmalnic G Wan KM Penman S Chromatin architecture and nuclear RNA Proceedings of the National Academy of Sciences of the United States of America January 1989 86 1 177 81 Bibcode 1989PNAS 86 177N PMC 286427 PMID 2911567 doi 10 1073 pnas 86 1 177 Ogawa Y Sun BK Lee JT Intersection of the RNA interference and X inactivation pathways Science June 2008 320 5881 1336 41 Bibcode 2008Sci 320 1336O PMC 2584363 PMID 18535243 doi 10 1126 science 1157676 Pagano JM Farley BM McCoig LM Ryder SP Molecular basis of RNA recognition by the embryonic polarity determinant MEX 5 The Journal of Biological Chemistry March 2007 282 12 8883 94 PMID 17264081 doi 10 1074 jbc M700079200 Pang KC Frith MC Mattick JS Rapid evolution of noncoding RNAs lack of conservation does not mean lack of function Trends in Genetics January 2006 22 1 1 5 PMID 16290135 doi 10 1016 j tig 2005 10 003 Panganiban G Rubenstein JL Developmental functions of the Distal less Dlx homeobox genes Development 1 October 2002 129 19 4371 86 2014 02 01 PMID 12223397 原始内容存档于2019 07 10 Pasmant E Laurendeau I Heron D Vidaud M Vidaud D Bieche I Characterization of a germ line deletion including the entire INK4 ARF locus in a melanoma neural system tumor family identification of ANRIL an antisense noncoding RNA whose expression coclusters with ARF Cancer Research April 2007 67 8 3963 9 PMID 17440112 doi 10 1158 0008 5472 CAN 06 2004 Pauler FM Koerner MV Barlow DP Silencing by imprinted noncoding RNAs is transcription the answer Trends in Genetics June 2007 23 6 284 92 PMID 17445943 doi 10 1016 j tig 2007 03 018 Pennacchio LA Ahituv N Moses AM et al In vivo enhancer analysis of human conserved non coding sequences Nature November 2006 444 7118 499 502 Bibcode 2006Natur 444 499P PMID 17086198 doi 10 1038 nature05295 引文格式1维护 显式使用等标签 link Perkel Jeffrey M Visiting Noncodarnia BioTechniques paper 使用 format 需要含有 url 帮助 2013 54 6 301 304 PMID 23750541 doi 10 2144 000114037 We re calling long noncoding RNAs a class when actually the only definition is that they are longer than 200 bp says Ana Marques a Research Fellow at the University of Oxford who uses evolutionary approaches to understand lncRNA function Pibouin L Villaudy J Ferbus D et al Cloning of the mRNA of overexpression in colon carcinoma 1 a sequence overexpressed in a subset of colon carcinomas Cancer Genetics and Cytogenetics February 2002 133 1 55 60 PMID 11890990 doi 10 1016 S0165 4608 01 00634 3 引文格式1维护 显式使用等标签 link Pollard KS Salama SR King B et al Forces shaping the fastest evolving regions in the human genome PLoS Genetics October 2006 2 10 e168 PMC 1599772 PMID 17040131 doi 10 1371 journal pgen 0020168 引文格式1维护 显式使用等标签 link Pollard KS Salama SR Lambert N et al An RNA gene expressed during cortical development evolved rapidly in humans Nature September 2006 443 7108 167 72 Bibcode 2006Natur 443 167P PMID 16915236 doi 10 1038 nature05113 引文格式1维护 显式使用等标签 link Ponjavic J Ponting CP Lunter G Functionality or transcriptional noise Evidence for selection within long noncoding RNAs Genome Research May 2007 17 5 556 65 PMC 1855172 PMID 17387145 doi 10 1101 gr 6036807 PMID 21047393 Reis EM Nakaya HI Louro R et al Antisense intronic non coding RNA levels correlate to the degree of tumor differentiation in prostate cancer Oncogene August 2004 23 39 6684 92 PMID 15221013 doi 10 1038 sj onc 1207880 引文格式1维护 显式使用等标签 link Rinn JL Kertesz M Wang JK et al Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs Cell June 2007 129 7 1311 23 PMC 2084369 PMID 17604720 doi 10 1016 j cell 2007 05 022 引文格式1维护 显式使用等标签 link Rodriguez Campos A Azorin F RNA is an integral component of chromatin that contributes to its structural organization PLoS ONE 2007 2 11 e1182 Bibcode 2007PLoSO 2 1182R PMC 2063516 PMID 18000552 doi 10 1371 journal pone 0001182 Sanchez Elsner T Gou D Kremmer E Sauer F Noncoding RNAs of trithorax response elements recruit Drosophila Ash1 to Ultrabithorax Science February 2006 311 5764 1118 23 Bibcode 2006Sci 311 1118S PMID 16497925 doi 10 1126 science 1117705 Schoeftner S Blasco MA Developmentally regulated transcription of mammalian telomeres by DNA dependent RNA polymerase II Nature Cell Biology February 2008 10 2 228 36 PMID 18157120 doi 10 1038 ncb1685 Shamovsky I Nudler E Gene control by large noncoding RNAs Science s STKE Signal Transduction Knowledge Environment October 2006 2006 355 pe40 PMID 17018852 doi 10 1126 stke 3552006pe40 Shamovsky I Nudler E Modular RNA heats up Molecular Cell February 2008 29 4 415 7 PMID 18313380 doi 10 1016 j molcel 2008 02 001 Shirasawa S Harada H Furugaki K et al SNPs in the promoter of a B cell specific antisense transcript SAS ZFAT determine susceptibility to autoimmune thyroid disease Human Molecular Genetics October 2004 13 19 2221 31 PMID 15294872 doi 10 1093 hmg ddh245 引文格式1维护 显式使用等标签 link Siepel A Bejerano G Pedersen JS et al Evolutionarily conserved elements in vertebrate insect worm and yeast genomes Genome Research August 2005 15 8 1034 50 PMC 1182216 PMID 16024819 doi 10 1101 gr 3715005 引文格式1维护 显式使用等标签 link Singh K Carey M Saragosti S Botchan M Expression of enhanced levels of small RNA polymerase III transcripts encoded by the B2 repeats in simian virus 40 transformed mouse cells Nature 1985 314 6011 553 6 Bibcode 1985Natur 314 553S PMID 2581137 doi 10 1038 314553a0 Sleutels F Zwart R Barlow DP The non coding Air RNA is required for silencing autosomal imprinted genes Nature February 2002 415 6873 810 3 PMID 11845212 doi 10 1038 415810a Smith NG Brandstrom M Ellegren H Evidence for turnover of functional noncoding DNA in mammalian genome evolution Genomics November 2004 84 5 806 13 PMID 15475259 doi 10 1016 j ygeno 2004 07 012 Sonkoly E Bata Csorgo Z Pivarcsi A et al Identification and characterization of a novel psoriasis susceptibility related noncoding RNA gene PRINS The Journal of Biological Chemistry June 2005 280 25 24159 67 PMID 15855153 doi 10 1074 jbc M501704200 引文格式1维护 显式使用等标签 link Struhl K Transcriptional noise and the fidelity of initiation by RNA polymerase II Nature Structural amp Molecular Biology February 2007 14 2 103 5 PMID 17277804 doi 10 1038 nsmb0207 103 Tang RB Wang HY Lu HY et al Increased level of polymerase III transcribed Alu RNA in hepatocellular carcinoma tissue Molecular Carcinogenesis February 2005 42 2 93 6 PMID 15593371 doi 10 1002 mc 20057 引文格式1维护 显式使用等标签 link Tiedge H Chen W Brosius J Primary structure neural specific expression and dendritic location of human BC200 RNA Journal of Neuroscience 1 June 1993 13 6 2382 90 2014 02 01 PMID 7684772 原始内容存档于2019 07 10 Tiedge H Fremeau RT Weinstock PH Arancio O Brosius J Dendritic location of neural BC1 RNA Proceedings of the National Academy of Sciences of the United States of America March 1991 88 6 2093 7 Bibcode 1991PNAS 88 2093T PMC 51175 PMID 1706516 doi 10 1073 pnas 88 6 2093 Torarinsson E Sawera M Havgaard JH Fredholm M Gorodkin J Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure Genome Research July 2006 16 7 885 9 PMC 1484455 PMID 16751343 doi 10 1101 gr 5226606 Torarinsson E Sawera M Havgaard JH Fredholm M Gorodkin J Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure Genome Research July 2006 16 7 885 9 PMC 1484455 PMID 16751343 doi 10 1101 gr 5226606 Tufarelli C Stanley JA Garrick D et al Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease Nature Genetics June 2003 34 2 157 65 PMID 12730694 doi 10 1038 ng1157 引文格式1维护 显式使用等标签 link Umlauf D Goto Y Cao R et al Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes Nature Genetics December 2004 36 12 1296 300 PMID 15516932 doi 10 1038 ng1467 引文格式1维护 显式使用等标签 link Visel A Prabhakar S Akiyama JA et al Ultraconservation identifies a small subset of extremely constrained developmental enhancers Nature Genetics February 2008 40 2 158 60 PMC 2647775 PMID 18176564 doi 10 1038 ng 2007 55 引文格式1维护 显式使用等标签 link Wang H Iacoangeli A Lin D et al Dendritic BC1 RNA in translational control mechanisms The Journal of Cell Biology December 2005 171 5 811 21 PMC 1828541 PMID 16330711 doi 10 1083 jcb 200506006 引文格式1维护 显式使用等标签 link Wang X Arai S Song X et al Induced ncRNAs allosterically modify RNA binding proteins in cis to inhibit transcription Nature July 2008 454 7200 126 30 Bibcode 2008Natur 454 126W PMC 2823488 PMID 18509338 doi 10 1038 nature06992 引文格式1维护 显式使用等标签 link Waterston RH Lindblad Toh K Birney E et al Initial sequencing and comparative analysis of the mouse genome Nature December 2002 420 6915 520 62 Bibcode 2002Natur 420 520W PMID 12466850 doi 10 1038 nature01262 引文格式1维护 显式使用等标签 link Wutz A Gribnau J X inactivation Xplained Current Opinion in Genetics amp Development October 2007 17 5 387 93 PMID 17869504 doi 10 1016 j gde 2007 08 001 Wutz A Rasmussen TP Jaenisch R Chromosomal silencing and localization are mediated by different domains of Xist RNA Nature Genetics February 2002 30 2 167 74 PMID 11780141 doi 10 1038 ng820 Yang S Tutton S Pierce E Yoon K Specific double stranded RNA interference in undifferentiated mouse embryonic stem cells Molecular and Cellular Biology November 2001 21 22 7807 16 PMC 99950 PMID 11604515 doi 10 1128 MCB 21 22 7807 7816 2001 Yik JH Chen R Nishimura R Jennings JL Link AJ Zhou Q Inhibition of P TEFb CDK9 Cyclin T kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA Molecular Cell October 2003 12 4 971 82 PMID 14580347 doi 10 1016 S1097 2765 03 00388 5 Yu W Gius D Onyango P et al Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA Nature January 2008 451 7175 202 6 Bibcode 2008Natur 451 202Y PMC 2743558 PMID 18185590 doi 10 1038 nature06468 引文格式1维护 显式使用等标签 link Zearfoss NR Chan AP Kloc M Allen LH Etkin LD Identification of new Xlsirt family members in the Xenopus laevis oocyte Mechanisms of Development April 2003 120 4 503 9 PMID 12676327 doi 10 1016 S0925 4773 02 00459 8 Zwart R Sleutels F Wutz A Schinkel AH Barlow DP Bidirectional action of the Igf2r imprint control element on upstream and downstream imprinted genes Genes amp Development September 2001 15 18 2361 6 PMC 312779 PMID 11562346 doi 10 1101 gad 206201 取自 https zh wikipedia org w index php title 长链非编码核糖核酸 amp oldid 72927651, 维基百科，wiki，书籍，书籍，图书馆，

文章

，阅读，下载，免费，免费下载，mp3，视频，mp4，3gp， jpg，jpeg，gif，png，图片，音乐，歌曲，电影，书籍，游戏，游戏。