Mining mammalian transcript data for functional long non-coding RNAs.
Mining mammalian transcript data for functional long non-coding RNAs.
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DOI：
10.1371/journal.pone.0010316
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发表时间：
2010-04-23
期刊：
影响因子：
3.7
通讯作者：
Harrison PM
中科院分区：
文献类型：
--
作者：
Khachane AN;Harrison PM
近年来，长链非编码RNA（lncRNA）在控制基因表达中的作用引起了越来越多的关注。测序项目，如小鼠的Fantom 3和人类的H-InvDB，已经产生了关于哺乳动物细胞转录成分的丰富数据，其中大部分似乎不是蛋白质编码。然而，许多非蛋白质编码转录组可能仅仅是“转录噪音”的结果。因此，使用生物信息学方法以高通量方式鉴定可能的功能候选物是至关重要的。我们推导出一个用于分类和注释哺乳动物中可能的功能lncRNA的方案。使用现有的实验全长cDNA数据集的人类和小鼠，我们确定了78 lncRNA，要么是人类和小鼠之间的同线保守，或来自相同的蛋白质编码基因。其中，11个具有显著的序列同源性。我们发现这些lncRNA表现出：（i）非编码转录物典型的密码子替换模式;（ii）在远距离哺乳动物如狗和牛中的序列保留;（iii）相对于它们相应的侧翼区域的显著序列保守性（在50%的情况下，侧翼区根本不具有同源性;在其余的情况下，保守程度明显更低）;（iv）主要以单外显子形式存在（8/11）;和（v）在它们内部存在保守和稳定的二级结构基序。我们进一步鉴定了对lncRNA库有贡献的正磷酸酶蛋白编码基因;其中，与癌发生有关的基因显著过量。我们的比较哺乳动物基因组学方法加上进化分析，确定了一个小群体的保守的长非蛋白编码RNA（lncRNA），是潜在的功能在哺乳动物。此外，我们的分析表明，在产生lncRNA的正向同源蛋白编码基因中，那些与癌症发病机制有关的基因明显过多，这表明这些lncRNA可能在癌症病理机制中发挥重要作用。
The role of long non-coding RNAs (lncRNAs) in controlling gene expression has garnered increased interest in recent years. Sequencing projects, such as Fantom3 for mouse and H-InvDB for human, have generated abundant data on transcribed components of mammalian cells, the majority of which appear not to be protein-coding. However, much of the non-protein-coding transcriptome could merely be a consequence of ‘transcription noise’. It is therefore essential to use bioinformatic approaches to identify the likely functional candidates in a high throughput manner. We derived a scheme for classifying and annotating likely functional lncRNAs in mammals. Using the available experimental full-length cDNA data sets for human and mouse, we identified 78 lncRNAs that are either syntenically conserved between human and mouse, or that originate from the same protein-coding genes. Of these, 11 have significant sequence homology. We found that these lncRNAs exhibit: (i) patterns of codon substitution typical of non-coding transcripts; (ii) preservation of sequences in distant mammals such as dog and cow, (iii) significant sequence conservation relative to their corresponding flanking regions (in 50% cases, flanking regions do not have homology at all; and in the remaining, the degree of conservation is significantly less); (iv) existence mostly as single-exon forms (8/11); and, (v) presence of conserved and stable secondary structure motifs within them. We further identified orthologous protein-coding genes that are contributing to the pool of lncRNAs; of which, genes implicated in carcinogenesis are significantly over-represented. Our comparative mammalian genomics approach coupled with evolutionary analysis identified a small population of conserved long non-protein-coding RNAs (lncRNAs) that are potentially functional across Mammalia. Additionally, our analysis indicates that amongst the orthologous protein-coding genes that produce lncRNAs, those implicated in cancer pathogenesis are significantly over-represented, suggesting that these lncRNAs could play an important role in cancer pathomechanisms.
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影响因子：
8.8
作者：
Davies, M. A.;Stemke-Hale, K.;Tellez, C.;Calderone, T. L.;Deng, W.;Prieto, V. G.;Lazar, A. J. F.;Gershenwald, J. E.;Mills, G. B.
通讯作者：
Mills, G. B.
影响因子：
9.8
作者：
Church DM;Goodstadt L;Hillier LW;Zody MC;Goldstein S;She X;Bult CJ;Agarwala R;Cherry JL;DiCuccio M;Hlavina W;Kapustin Y;Meric P;Maglott D;Birtle Z;Marques AC;Graves T;Zhou S;Teague B;Potamousis K;Churas C;Place M;Herschleb J;Runnheim R;Forrest D;Amos-Landgraf J;Schwartz DC;Cheng Z;Lindblad-Toh K;Eichler EE;Ponting CP;Mouse Genome Sequencing Consortium
通讯作者：
Mouse Genome Sequencing Consortium
影响因子：
3.5
作者：
Buim, ME;Soares, FA;Nagai, MA
通讯作者：
Nagai, MA
影响因子：
56.9
作者：
Kapranov, Philipp;Cheng, Jill;Gingeras, Thomas R.
通讯作者：
Gingeras, Thomas R.
影响因子：
56.9
作者：
Duret, L;Chureau, C;Avner, P
通讯作者：
Avner, P