長鏈非編碼RNA

(重定向自大型非编码RNA
跳轉到: 導航, 搜索

長鏈非編碼RNA類英語:Long non-coding RNAs,簡稱為lncRNA)指的是長於200核苷酸的不編碼蛋白質轉錄物Perkel 2013)。該有些武斷的界定將長鏈非編碼RNA類與較小的調控RNA類區分開來,後者如微RNA類(miRNAs)、小干擾RNA類(siRNAs)、Piwi互作RNA類(piRNAs)、小核仁RNA類(snoRNAs)及其它短RNA類(Ma 2013)。

目錄

長鏈非編碼RNA類的丰度

近年研究顯示人類基因組中的轉錄只有五分之一與蛋白編碼基因有關(Kapranov 2007),這說明至少有較編碼RNA序列四倍多的長鏈非編碼RNA。而像FANTOM(哺乳動物cDNA功能注釋)等的大規模互補DNA(cDNA)測序計劃揭示了轉錄的複雜性(Carninci 2005)。FANTOM3計劃從約一萬個不同的基因座中鑒定出了約三萬五千條非編碼轉錄物它們有著與mRNA類類似的特徵,包括5'端有帽、受到剪接多聚腺苷酸化,但只有很小的開放閱讀框(ORF)或根本沒有(Carninci 2005)。然而長鏈非編碼RNA的丰度是意料之外的,其數目代表的是保守估計的最低值,因為這種方法忽略了許多單獨的轉錄物及非多腺苷酸化的轉錄物(瓦片陣列數據顯示出40%以上的轉錄物是非多腺苷酸化的)(Cheng 2005)。儘管如此,在這些cDNA文庫中明確鑒定非編碼RNA類仍是充滿挑戰的,因為該方法無法區分非編碼轉錄物及蛋白編碼轉錄物。

長鏈非編碼RNA類的基因組組織

目前將哺乳動物基因組的全景描繪為:長段的基因間空間將多個轉錄「焦點」分割開(Carninci 2005)。然而長鏈非編碼RNA類正位於這些基因間區段中並由此轉錄出來,其中大多數是與其它轉錄物之間呈錯綜複雜的正義或反義重疊,這些轉錄物往往包括了蛋白編碼基因(Kapranov 2007)。在正義或反義鏈上的多個不同的編碼或非編碼轉錄物共享這些轉錄焦點中的基因組序列(Birney 2007),使得這些重疊的亞型之間產生複雜的層次結構。例如,8961個cDNA中的3012個曾被FANTOM2計劃注釋為編碼序列中的一段截短序列,但後來又重新被指定為蛋白編碼cDNA中的新非編碼RNA變異體Carninci 2005)。儘管編碼RNA及非編碼RNA的交錯排列具備一定的丰度和保守性,並可能意味著它們兩者之間具有某些生物學關聯性,但仍無法對這些複雜的焦點結構進行簡單的評價。

GENCODE共同體已綜合性整理及分析了一些人類長鏈非編碼RNA的注釋及它們的基因組結構、修飾、細胞定位及組織表達譜(Derrien 2012)。他們的分析結果說明人類長鏈非編碼RNA易形成具有兩個外顯子的轉錄物(Derrien 2012)。

轉錄因子調控的長鏈非編碼RNA類

如lncRNA晶片及RNA-Seq等高通量基因組技術往往會產生一系列令人感興趣的長鏈非編碼RNA,但對於這些長鏈非編碼RNA基因所受的轉錄調控卻知之甚少。根據來自ENCODE計劃的轉錄因子(TFs)ChIP-Seq峰值列表和來自GENCODE的已注釋人類長鏈非編碼RNA,哈爾濱工業大學的研究團隊開發了一個基於網路界面的軟體——TF2lncRNA, High-throughput genomic technologies like lncRNA microarray and RNA-Seq often generate a set of lncRNAs of interest, yet little is known about the transcriptional regulation of the set of lncRNA genes. Here, based on ChIP-Seq peak lists of transcription factors (TFs) from ENCODE and annotated human lncRNAs from GENCODE, we developed a web-based interface titled 『TF2lncRNA』, where TF peaks from each ChIP-Seq experiment are crossed with the genomic coordinates of a set of input lncRNAs, to identify which TFs present a statistically significant number of binding sites (peaks) within the regulatory region of the input lncRNA genes. The input can be a set of co-expressed lncRNA genes, or any other cluster of lncRNA genes. Users can thus infer which TFs are likely to be common transcription regulators of the set of lncRNAs. In addition, users can retrieve all lncRNAs potentially regulated by a specific TF in a specific cell line of interest, or retrieve all TFs that have one or more binding sites in the regulatory region of a given lncRNA in the specific cell line. TF2LncRNA is an efficient and easy-to-use web-based tool accessible at http://mlg.hit.edu.cn/tf2lncrna.

長鏈非編碼RNA類的保守性

如微RNA類及小核仁RNA類等的眾多小型RNA類都顯現出了跨多物種保守性Bentwich 2005)。與之相反,大多數長鏈非編碼RNA則保守性不強,這一點常被引用為其不具備功能的證據(Brosius 2005Struhl 2007)。然而,如AirXist等經過詳細研究的長鏈非編碼RNA,它們的保守性也很差(Nesterova 2001),這意味著非編碼RNA類可能受到不同的選擇壓力Pang 2006)。mRNA必須保守密碼子的正常用法並防止單個長ORF中出現移碼突變,然而對長鏈非編碼RNA的選擇壓力可能只會令其保守其中的較短區域,這些較短區域對於結構或序列特異性相互作用較為關鍵。因此,我們可見選擇壓力只會作用於長鏈非編碼RNA轉錄物的小塊區域。仍然要看到:儘管長鏈非編碼RNA總體來說保守性較低,但仍可見許多長鏈非編碼RNA具有較強的保守元件。例如,高度保守的phastCons元件中有19%存在於已知的內含子中,而其它32%存在於未注釋的區域之中(Siepel 2005)。此外,人類長鏈非編碼RNA中的具有代表性的一類長鏈非編碼RNA在鹼基取代和插入/缺失速率方面顯現出較小但顯著的降低,這一現象指示了淨化選擇壓力使得轉錄物的完整性得到保守,這在序列、啟動子及剪接三種水平上體現出來(Ponjavic 2007)。

非編碼RNA的保守性差可能是近期且快速的適應性選擇的結果。例如,非編碼RNA類較蛋白編碼基因可能對進化壓力可塑性更強,如XistAir等的許多世系特異性非編碼RNA的存在可以證明這一點(Pang 2006)。相對於黑猩猩基因組來說人類基因組中經受近期進化改變的保守區域確實主要存在於非編碼區域,其中很多已有詳盡描述(Pollard 2006Pollard 2006)。其中包括一條名為HAR1F的非編碼RNA,該基因在人類中經歷了快速的進化變化,且特異性地在人類新皮質的卡哈爾-雷濟厄斯氏細胞中特異性表達(Pollard 2006)。現有報導稱許多功能已確定的RNA進化速率也很快(Pang 2006Smith 2004),這可能由於這些序列受到結構-功能約束時表現得更靈活,我們可以期待在這些序列中發現新的進化方式。人類基因組中有數千條序列的一級序列保守性較差,但有證據顯示它們RNA二級結構卻存在著保守性(Torarinsson 2006Torarinsson 2008),這支持了上述論點。

長鏈非編碼RNA類的功能

cDNA文庫的大規模測序及更先進的基於下一代測序的轉錄組測序表明哺乳動物中長鏈非編碼RNA的數量大約是幾萬條。然而,雖然越來越多的證據提示大多數長鏈非編碼RNA具有功能(Mercer 2009Dinger 2009),但相對只有一小部分已被證明有生物學重大意義。截至2012年十二月,約有127條長鏈非編碼RNA在LncRNAdb(一個描述長鏈非編碼RNA的文獻資料庫)中有功能注釋(Amral 2011)。

長鏈非編碼RNA類在基因轉錄調控中的作用

長鏈非編碼RNA類在基因特異性轉錄中的作用

RNA轉錄在真核生物中是一個受到嚴密調控的過程。非編碼RNA可以靶向該進程的多個方面,包括靶向轉錄激活因子或轉錄抑制因子、如RNA聚合酶(RNAP)Ⅱ等轉錄反應中的各組分、甚至是DNA螺旋結構,以達到調控基因轉錄及表達的目的(Goodrich 2006)。非編碼RNA將這些機制結合在一起可以組成為一個包括轉錄因子在內的調控網路,可以精細地調控複雜真核生物的基因表達

非編碼RNA通過多種不同的機制調節轉錄因子的功能,包括充當共調控因子的角色、修飾轉錄因子的活性或是調控共調控因子的活性。例如,非編碼RNA Evf-2作為同源異形框轉錄因子Dlx2的共激活因子,Dlx2在前腦發育及神經發生中起到重要作用(Feng 2006Panganiban 2002)。Evf-2轉錄自位於DLX5|Dlx5DLX6|Dlx6基因之間的超保守元件,音蝟因子在前腦發育過程中誘導該長鏈的轉錄(Feng 2006)。Evf-2接著將Dlx2轉錄因子招募到同一個超保守元件處,Dlx2在此處誘導Dlx5的表達。哺乳動物基因組中存在其它一些可轉錄且執行增強子功能的超級保守或高度保守元件,這提示Evf-2可作為範例闡述脊椎動物生長過程中以複雜表達的形式嚴密調控重要發育基因的普遍機制(Pennacchio 2006Visel 2008)。近期研究也確實發現與之類似的其它非編碼超保守元件的轉錄及表達在人類白血病中出現異常,且促進結腸癌細胞凋亡,這提示了它們涉及到腫瘤形成(Calin 2007)。

局部的非編碼RNA類可以招募轉錄機制對附近蛋白編碼基因的轉錄加以調控。TLS(英語:translocated in liposarcoma)是一種結合RNA的蛋白,它結合到CREB結合蛋白組蛋白醯基轉移酶p300上並抑制這兩者在靶基因周期蛋白D1上的活性,從而起到抑制後者的作用。作為DNA受損信號的響應,長鏈非編碼RNA以低水平表達出來並拴在周期蛋白D1基因的5'調控區域上,這指導了TLS招募到周期蛋白D1啟動子上(Wang 2008)。除此之外,這些局部的非編碼RNA作為配體調控TLS的活性。從更廣泛的層面上說,這一機制使得細胞可以利用RNA結合蛋白(它們組成了哺乳動物蛋白質組中的最龐大的種類之一)並在轉錄程序控制中整合它們的功能。

在X染色體失活的情況下一些基因仍可以轉錄,近期對逃避染色體失活控制的染色體區域進行研究,發現其中表達的長鏈非編碼RNA可能介導了這一過程(Reinius 2010)。

長鏈非編碼RNA調控基礎轉錄機器

非編碼RNA還可以靶向通用轉錄因子,後者是RNAPⅡ轉錄所有基因所必需的(Goodrich 2006)。這些通用因子包括了起始複合體中組裝在啟動子上或涉及轉錄延伸的部件。轉錄自二氫葉酸還原酶DHFR)基因上游次要啟動子的一條非編碼RNA進入DHFR主要啟動子,形成穩定的RNA-DNA三股螺旋以阻止轉錄輔因子TFⅡB結合到其上(Martianov 2007)。已知真核染色體上存在著數千個三股螺旋(Lee 1987),這一調控基因表達的新機制可能事實上代表這些三股螺旋在控制啟動子上起到的廣泛作用。U1非編碼RNA通過結合到TFⅡH上並刺激其對RNAPⅡ的C-端以實現誘導轉錄起始(Kwek 2002)。相反,非編碼RNA 7SK可通過下列方式起到抑制轉錄延伸的作用:7SK首先與HEXIM1/2結合,形成抑制性複合物,該複合物阻止PTEFb通用轉錄因子去磷酸化RNAPⅡ的C-端結構域Kwek 2002Yang 2001Yik 2003),當細胞處於應激狀況下可以抑制全局延伸。這些例子中的機制可以繞開單個啟動子上特異性的調控模式,介導起始及延伸轉錄機器工作水平發生直接改變,提供了迅速影響基因表達全局改變的方法。

現也證明非編碼重複序列有著介導全局調控的能力。人類的短散在核內(SINE)Alu元件及小鼠中同源的B1和B2元件是基因組中丰度最高的可移動性元件,分別組成了人類和小鼠基因組的約10%和約6%(Lander 2001Waterston 2002)。在如熱休克等環境應激情況下這些元件被RNAPⅢ轉錄為非編碼RNA(Liu 1995),後者接下來會以高親和度的方式與RNAPⅡ結合併阻止其形成為有活性的前起始複合物Allen 2004Espinoza 2004Espinoza 2007Mariner & Walters 2008)。這使得在響應應激的情況下可以大範圍並迅速抑制基因的表達(Allen 2004Mariner & Walters 2008)。

對Alu元件的RNA轉錄物中的功能序列進行分析後,發現其亦有類似於蛋白質轉錄因子中結構域的模塊化結構(Shamovsky 2008)。Alu元件RNA包括兩個「臂」,每個臂都可以結合到一個RNAPⅡ分子上;體外實驗表明該RNA還具有兩個調控結構域,起到抑制RNAPⅡ轉錄活性的作用(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).

除了熱休克外,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.

長鏈非編碼RNA類在基因轉錄後調控中的作用

In addition to regulating transcription, ncRNAs also control various aspects of post-transcriptional mRNA processing. Similar to small regulatory RNAs such as microRNAs and snoRNAs, these functions often involve complementary base pairing with the target mRNA. The formation of RNA duplexes between complementary ncRNA and mRNA may mask key elements within the mRNA required to bind trans-acting factors, potentially effecting any step in post-transcriptional gene expression including pre-mRNA processing and splicing, transport, translation, and degradation.

長鏈非編碼RNA類在剪接調控中的作用

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).

長鏈非編碼RNA類在翻譯調控中的作用

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).

長鏈非編碼RNA類在siRNA導向的基因調控中的作用

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).

長鏈非編碼RNA類在表觀遺傳調控中的作用

包括組蛋白和DNA甲基化、組蛋白乙醯化和SUMO化等在內的表觀遺傳修飾影響了染色體生物學的眾多方面,主要包括通過對廣大染色質區域進行重塑從而調控大量基因(Kiefer 2007Mikkelsen 2007)。一段時間以來,RNA作為染色質的有機組成部分已被人知曉(Nickerson 1989Rodriguez-Campos 2007),但現在我們才開始認識到RNA在涉及到染色質修飾通路上的意義(Chen 2008Rinn 2007Sanchez-Elsner 2006)。

果蠅屬中的長鏈非編碼RNA類通過將三胸蛋白Ash1募集到同源異形調控元件並指導其發揮染色質修飾作用的方式誘導同源異形基因Ubx的表達(Sanchez-Elsner 2006)。後來發現哺乳動物中也存在著相似的調控模式:認為強大的表觀遺傳機制奠定了胚胎同源異形基因家族的表達譜,而同源異形基因家族是貫穿整個人體發育過程中持續發揮作用的重要因子(Mazo 2007Rinn 2007)。人類同源異形基因家族確實與數百個非編碼RNA之間有著相關性,這些非編碼RNA在人體發育的時空軸上按順序表達,這些非編碼RNA也定義染色質各區域中組蛋白甲基化程度的差異以及RNA聚合酶可進入染色質的程度(Rinn 2007)。其中一條名為HOTAIR的轉錄自HOXC基因座的非編碼RNA通過改變組蛋白三甲基化狀態從而使HOXD基因座中長約40kb的區域發生轉錄沉默。目前認為HOTAIR執行的作用機制是:多梳染色質重塑複合物具有操縱細胞表觀遺傳狀態的功能,而HOTAIR以反式調控的方式指導該功能的發揮並繼而影響基因的表達。多梳複合物中的成員包括SUZ12、EZH2和EED等,它們具有RNA結合結構域並可能結合HOTAIR及其它類似的非編碼RNA類(Denisenko 1998Katayama 2005)。該例子極好地描繪出了這樣一個更廣泛的主題:非編碼RNA類招募一系列染色質修飾蛋白到特定基因組基因座上並發揮功能,這更加突出了目前所繪製基因組圖譜的複雜性(Mikkelsen 2007)。發育時期中調控基因表達的染色質修飾有著區域化的模式,大量長鏈非編碼與蛋白編碼基因的聯繫確實幫助塑造了這種模式。例如,大多數蛋白編碼基因都具有配對的反義基因,許多抑癌基因癌症中常受到沉默,一些反義基因使用表觀遺傳機制使這些抑癌基因沉默(Yu 2008)。近期研究發現:在白血病中p15基因和一條反義非編碼RNA的表達此消彼長(Yu 2008)。經過詳細分析發現:p15的反義非編碼RNA(CDKN2BAS)可通過一種未知機制誘導p15異染色質和DNA甲基化狀態發生改變,因而調控了p15基因的表達(Yu 2008)。因此,相關的反義非編碼RNA類表達發生異常可能繼而沉默了抑癌基因,從而走向癌症發生。

基因印記

最近非編碼RNA指導的染色質修飾主題最初是從基因組印記的現象中引出的,基因組印記是僅從母系或父系染色體兩者中的一個表達出等位基因的現象。一般來說,印記基因是呈簇狀排列於染色體上,這提示:印記的機制是作用於局部的染色質區域上而不是針對單個基因。這些基因簇常常與長鏈非編碼RNA相關:長鏈非編碼RNA的表達量與在相同等位上相連鎖的蛋白編碼基因受到抑制的程度呈正相關Pauler 2007)。詳細分析確實顯示出非編碼RNA Kcnqot1Igf2r/Air在指導基因印記上發揮著重要作用(Braidotti 2004)。

幾乎所有位於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與X-染色體失活

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.

端粒非編碼RNA類

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.

長鏈非編碼RNA類在衰老與疾病中的作用

外部連結

另見

參考文獻

  • 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. doi:10.1038/ng1478. PMID 15565108. 
  • PubMed
  • 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. doi:10.1126/science.1147182. PMID 17916692. 
  • Beltran M, Puig I, Peña C, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2275429/ A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition]. Genes & Development. March 2008, 22 (6): 756–69. doi:10.1101/gad.455708. PMID 18347095. PMC 2275429. 
  • 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. doi:10.1038/ng1590. PMID 15965474. 
  • Birney E, Stamatoyannopoulos JA, Dutta A, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2212820/ Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project]. Nature. June 2007, 447 (7146): 799–816. doi:10.1038/nature05874. PMID 17571346. PMC 2212820. 
  • Blasco MA. Telomere length, stem cells and aging. Nature Chemical Biology. October 2007, 3 (10): 640–9. doi:10.1038/nchembio.2007.38. PMID 17876321. 
  • 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. doi:10.1101/sqb.2004.69.55. PMID 16117633. 
  • 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. doi:10.1093/hmg/ddm352. PMID 18048406. 
  • Brosius J. Waste not, want not--transcript excess in multicellular eukaryotes. Trends in Genetics. May 2005, 21 (5): 287–8. doi:10.1016/j.tig.2005.02.014. PMID 15851065. 
  • 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. doi:10.1016/j.ccr.2007.07.027. PMID 17785203. 
  • Carninci P, Kasukawa T, Katayama S, et al.. The transcriptional landscape of the mammalian genome. Science. September 2005, 309 (5740): 1559–63. doi:10.1126/science.1112014. PMID 16141072. 
  • 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. doi:10.1523/JNEUROSCI.0548-07.2007. PMID 17699670. 
  • 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. doi:10.1016/j.cell.2008.04.043. PMID 18555785. 
  • 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. doi:10.1126/science.1108625. PMID 15790807. 
  • Costanzi C, Pehrson JR. Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature. June 1998, 393 (6685): 599–601. doi:10.1038/31275. PMID 9634239. 
  • Czech B, Malone CD, Zhou R, et al.. An endogenous small interfering RNA pathway in Drosophila. Nature. June 2008, 453 (7196): 798–802. doi:10.1038/nature07007. PMID 18463631. 
  • 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. PMID 9742080. PMC 109149. 
  • PubMed
  • 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. doi:10.1016/j.tig.2007.09.001. PMID 17977614. 
  • PubMed
  • Eis PS, Tam W, Sun L, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC552785/ 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. doi:10.1073/pnas.0500613102. PMID 15738415. PMC 552785. 
  • 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. doi:10.1038/nsmb812. PMID 15300239. 
  • Espinoza CA, Goodrich JA, Kugel JF. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1831867/ 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. doi:10.1261/rna.310307. PMID 17307818. PMC 1831867. 
  • Faghihi MA, Modarresi F, Khalil AM, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2826895/ 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. doi:10.1038/nm1784. PMID 18587408. PMC 2826895. 
  • Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1475760/ 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. doi:10.1101/gad.1416106. PMID 16705037. PMC 1475760. 
  • Fournier C, Goto Y, Ballestar E, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC136958/ Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes]. The EMBO Journal. December 2002, 21 (23): 6560–70. doi:10.1093/emboj/cdf655. PMID 12456662. PMC 136958. 
  • 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. doi:10.1089/dna.2006.25.135. PMID 16569192. 
  • Golden DE, Gerbasi VR, Sontheimer EJ. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2675693/ An inside job for siRNAs]. Molecular Cell. August 2008, 31 (3): 309–12. doi:10.1016/j.molcel.2008.07.008. PMID 18691963. PMC 2675693. 
  • Goodrich JA, Kugel JF. Non-coding-RNA regulators of RNA polymerase II transcription. Nature Reviews Molecular Cell Biology. August 2006, 7 (8): 612–6. doi:10.1038/nrm1946. PMID 16723972. 
  • Hesman Saey, Tina. Missing Lincs. Science News. 17 December 2011, 180 (13): 22–25. 
  • 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. doi:10.1007/s10038-006-0070-9. PMID 17066261. 
  • 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. doi:10.1161/ATVBAHA.109.189522. PMID 19592466. 
  • 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. doi:10.1126/science.1138341. PMID 17510325. 
  • Kapranov P, Willingham AT, Gingeras TR. Genome-wide transcription and the implications for genomic organization. Nature Reviews. Genetics. June 2007, 8 (6): 413–23. doi:10.1038/nrg2083. PMID 17486121. 
  • 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. doi:10.1186/1741-7007-8-149. PMID 21176148. PMC 3022773.  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. doi:10.1126/science.1112009. PMID 16141073. 
  • Kiefer JC. Epigenetics in development. Developmental Dynamics. April 2007, 236 (4): 1144–56. doi:10.1002/dvdy.21094. PMID 17304537. 
  • Kim. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2811656/ Evidence for bacterial origin of heat shock RNA-1]. RNA. February 2010, 16 (2): 274–279. doi:10.1261/rna.1879610. PMID 20040589. PMC 2811656. 
  • 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. doi:10.1038/nsb862. PMID 12389039. 
  • Lander ES, Linton LM, Birren B, et al.. Initial sequencing and analysis of the human genome. Nature. February 2001, 409 (6822): 860–921. doi:10.1038/35057062. PMID 11237011. 
  • Lee JS, Burkholder GD, Latimer LJ, Haug BL, Braun RP. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC340507/ A monoclonal antibody to triplex DNA binds to eucaryotic chromosomes]. Nucleic Acids Research. February 1987, 15 (3): 1047–61. doi:10.1093/nar/15.3.1047. PMID 2434928. PMC 340507. 
  • 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. doi:10.1016/j.bbr.2004.02.015. PMID 15302134. 
  • Li J, Witte DP, Van Dyke T, Askew DS. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1858164/ Expression of the putative proto-oncogene His-1 in normal and neoplastic tissues]. The American Journal of Pathology. April 1997, 150 (4): 1297–305. PMID 9094986. PMC 1858164. 
  • 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. doi:10.1038/sj.onc.1209846. PMID 16878148. 
  • lincRNA homepage of the Rinn Lab
  • Liu WM, Chu WM, Choudary PV, Schmid CW. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC306933/ Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts]. Nucleic Acids Research. May 1995, 23 (10): 1758–65. doi:10.1093/nar/23.10.1758. PMID 7784180. PMC 306933. 
  • Liu Y, Sanoff HK, Cho H, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2660422/ INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis]. PloS One. April 2009, 4 (4): e5027. doi:10.1371/journal.pone.0005027. PMID 19343170. PMC 2660422. 
  • Mancini-Dinardo D, Steele SJ, Levorse JM, Ingram RS, Tilghman SM. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1472902/ Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes]. Genes & Development. May 2006, 20 (10): 1268–82. doi:10.1101/gad.1416906. PMID 16702402. PMC 1472902. 
  • 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. doi:10.1016/j.molcel.2007.12.013. PMID 18313387. 
  • 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. doi:10.1038/nature05519. PMID 17237763. 
  • Mattick JS. Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. BioEssays. October 2003, 25 (10): 930–9. doi:10.1002/bies.10332. PMID 14505360. 
  • 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. doi:10.1242/jcs.007633. PMID 17690303. 
  • McPherson R, Pertsemlidis A, Kavaslar N , et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2711874/ A Common Allele on Chromosome 9 Associated with Coronary Heart Disease]. Science. May 2007, 316 (5830): 1488–91. doi:10.1126/science.1142447. PMID 17478681. PMC 2711874. 
  • PubMed
  • Mikkelsen TS, Ku M, Jaffe DB, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2921165/ Genome-wide maps of chromatin state in pluripotent and lineage-committed cells]. Nature. August 2007, 448 (7153): 553–60. doi:10.1038/nature06008. PMID 17603471. PMC 2921165. 
  • 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. doi:10.1093/hmg/8.7.1209. PMID 10369866. 
  • Mohammad F, Pandey RR, Nagano T, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2423283/ Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region]. Molecular and Cellular Biology. June 2008, 28 (11): 3713–28. doi:10.1128/MCB.02263-07. PMID 18299392. PMC 2423283. 
  • Morey C, Navarro P, Debrand E, Avner P, Rougeulle C, Clerc P. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1271805/ 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. doi:10.1038/sj.emboj.7600071. PMID 14749728. PMC 1271805. 
  • 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. PMID 1657988. 
  • Muslimov IA, Banker G, Brosius J, Tiedge H. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1828539/ Activity-dependent regulation of dendritic BC1 RNA in hippocampal neurons in culture]. The Journal of Cell Biology. June 1998, 141 (7): 1601–11. doi:10.1083/jcb.141.7.1601. PMID 9647652. PMC 1828539. 
  • 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. doi:10.1006/dbio.2001.0295. PMID 11437441. 
  • Nickerson JA, Krochmalnic G, Wan KM, Penman S. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC286427/ Chromatin architecture and nuclear RNA]. Proceedings of the National Academy of Sciences of the United States of America. January 1989, 86 (1): 177–81. doi:10.1073/pnas.86.1.177. PMID 2911567. PMC 286427. 
  • Ogawa Y, Sun BK, Lee JT. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2584363/ Intersection of the RNA interference and X-inactivation pathways]. Science. June 2008, 320 (5881): 1336–41. doi:10.1126/science.1157676. PMID 18535243. PMC 2584363. 
  • 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. doi:10.1074/jbc.M700079200. PMID 17264081. 
  • 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. doi:10.1016/j.tig.2005.10.003. PMID 16290135. 
  • Panganiban G, Rubenstein JL. Developmental functions of the Distal-less/Dlx homeobox genes. Development. 1 October 2002, 129 (19): 4371–86. PMID 12223397. 
  • 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. doi:10.1158/0008-5472.CAN-06-2004. PMID 17440112. 
  • Pauler FM, Koerner MV, Barlow DP. Silencing by imprinted noncoding RNAs: is transcription the answer?. Trends in Genetics. June 2007, 23 (6): 284–92. doi:10.1016/j.tig.2007.03.018. PMID 17445943. 
  • 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. doi:10.1038/nature05295. PMID 17086198. 
  • Perkel, Jeffrey M.. Visiting "Noncodarnia" (paper). BioTechniques. 2013, 54 (6): 301–304. doi:10.2144/000114037. PMID 23750541. ""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. doi:10.1016/S0165-4608(01)00634-3. PMID 11890990. 
  • Pollard KS, Salama SR, King B, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1599772/ Forces shaping the fastest evolving regions in the human genome]. PLoS Genetics. October 2006, 2 (10): e168. doi:10.1371/journal.pgen.0020168. PMID 17040131. PMC 1599772. 
  • 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. doi:10.1038/nature05113. PMID 16915236. 
  • Ponjavic J, Ponting CP, Lunter G. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1855172/ Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs]. Genome Research. May 2007, 17 (5): 556–65. doi:10.1101/gr.6036807. PMID 17387145. PMC 1855172. 
  • PubMed
  • 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. doi:10.1038/sj.onc.1207880. PMID 15221013. 
  • Rinn JL, Kertesz M, Wang JK, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2084369/ Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs]. Cell. June 2007, 129 (7): 1311–23. doi:10.1016/j.cell.2007.05.022. PMID 17604720. PMC 2084369. 
  • Rodríguez-Campos A, Azorín F. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2063516/ RNA is an integral component of chromatin that contributes to its structural organization]. PLoS ONE. 2007, 2 (11): e1182. doi:10.1371/journal.pone.0001182. PMID 18000552. PMC 2063516. 
  • 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. doi:10.1126/science.1117705. PMID 16497925. 
  • 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. doi:10.1038/ncb1685. PMID 18157120. 
  • Shamovsky I, Nudler E. Gene control by large noncoding RNAs. Science's STKE : Signal Transduction Knowledge Environment. October 2006, 2006 (355): pe40. doi:10.1126/stke.3552006pe40. PMID 17018852. 
  • Shamovsky I, Nudler E. Modular RNA heats up. Molecular Cell. February 2008, 29 (4): 415–7. doi:10.1016/j.molcel.2008.02.001. PMID 18313380. 
  • 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. doi:10.1093/hmg/ddh245. PMID 15294872. 
  • Siepel A, Bejerano G, Pedersen JS, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1182216/ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes]. Genome Research. August 2005, 15 (8): 1034–50. doi:10.1101/gr.3715005. PMID 16024819. PMC 1182216. 
  • 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. doi:10.1038/314553a0. PMID 2581137. 
  • 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. doi:10.1038/415810a. PMID 11845212. 
  • Smith NG, Brandström M, Ellegren H. Evidence for turnover of functional noncoding DNA in mammalian genome evolution. Genomics. November 2004, 84 (5): 806–13. doi:10.1016/j.ygeno.2004.07.012. PMID 15475259. 
  • 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. doi:10.1074/jbc.M501704200. PMID 15855153. 
  • Struhl K. Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nature Structural & Molecular Biology. February 2007, 14 (2): 103–5. doi:10.1038/nsmb0207-103. PMID 17277804. 
  • 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. doi:10.1002/mc.20057. PMID 15593371. 
  • 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. PMID 7684772. 
  • Tiedge H, Fremeau RT, Weinstock PH, Arancio O, Brosius J. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC51175/ 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. doi:10.1073/pnas.88.6.2093. PMID 1706516. PMC 51175. 
  • Torarinsson E, Sawera M, Havgaard JH, Fredholm M, Gorodkin J. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1484455/ Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure]. Genome Research. July 2006, 16 (7): 885–9. doi:10.1101/gr.5226606. PMID 16751343. PMC 1484455. 
  • Torarinsson E, Sawera M, Havgaard JH, Fredholm M, Gorodkin J. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1484455/ Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure]. Genome Research. July 2006, 16 (7): 885–9. doi:10.1101/gr.5226606. PMID 16751343. PMC 1484455. 
  • 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. doi:10.1038/ng1157. PMID 12730694. 
  • 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. doi:10.1038/ng1467. PMID 15516932. 
  • Visel A, Prabhakar S, Akiyama JA, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2647775/ Ultraconservation identifies a small subset of extremely constrained developmental enhancers]. Nature Genetics. February 2008, 40 (2): 158–60. doi:10.1038/ng.2007.55. PMID 18176564. PMC 2647775. 
  • Wang H, Iacoangeli A, Lin D, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1828541/ Dendritic BC1 RNA in translational control mechanisms]. The Journal of Cell Biology. December 2005, 171 (5): 811–21. doi:10.1083/jcb.200506006. PMID 16330711. PMC 1828541. 
  • Wang X, Arai S, Song X, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2823488/ Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription]. Nature. July 2008, 454 (7200): 126–30. doi:10.1038/nature06992. PMID 18509338. PMC 2823488. 
  • 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. doi:10.1038/nature01262. PMID 12466850. 
  • Wutz A, Gribnau J. X inactivation Xplained. Current Opinion in Genetics & Development. October 2007, 17 (5): 387–93. doi:10.1016/j.gde.2007.08.001. PMID 17869504. 
  • 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. doi:10.1038/ng820. PMID 11780141. 
  • Yang S, Tutton S, Pierce E, Yoon K. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC99950/ Specific double-stranded RNA interference in undifferentiated mouse embryonic stem cells]. Molecular and Cellular Biology. November 2001, 21 (22): 7807–16. doi:10.1128/MCB.21.22.7807-7816.2001. PMID 11604515. PMC 99950. 
  • 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. doi:10.1016/S1097-2765(03)00388-5. PMID 14580347. 
  • Yu W, Gius D, Onyango P, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2743558/ Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA]. Nature. January 2008, 451 (7175): 202–6. doi:10.1038/nature06468. PMID 18185590. PMC 2743558. 
  • 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. doi:10.1016/S0925-4773(02)00459-8. PMID 12676327. 
  • Zwart R, Sleutels F, Wutz A, Schinkel AH, Barlow DP. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC312779/ Bidirectional action of the Igf2r imprint control element on upstream and downstream imprinted genes]. Genes & Development. September 2001, 15 (18): 2361–6. doi:10.1101/gad.206201. PMID 11562346. PMC 312779. 


參考來源

關於「長鏈非編碼RNA」的留言: Feed-icon.png 訂閱討論RSS

目前暫無留言

添加留言

更多醫學百科條目

個人工具
名字空間
動作
導航
功能菜單
工具箱