Long noncoding RNA genes: conservation of sequence and brain expression among diverse amniotes.
Long noncoding RNA genes: conservation of sequence and brain expression among diverse amniotes.
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DOI：
10.1186/gb-2010-11-7-r72
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发表时间：
2010
期刊：
影响因子：
12.3
通讯作者：
Ponting CP
中科院分区：
文献类型：
--
作者：
Chodroff RA;Goodstadt L;Sirey TM;Oliver PL;Davies KE;Green ED;Molnár Z;Ponting CP
长期以来，蛋白质被认为是生命的基石，现在很明显，蛋白质只是真核生物基因组产生的许多功能性产物之一。事实上，人类基因组转录成非编码序列的部分比转录成蛋白质编码序列的部分要多。然而，尽管我们已经对蛋白质编码序列的进化约束和功能之间的关系有了深入的了解，但对非编码转录序列的这些关系知之甚少。这种信息的缺乏部分是由于在序列和表达数据库中缺乏鸟类和哺乳动物中已建立的非蛋白编码RNA （ncRNA）同源物。在这里，我们进行了一项多学科研究，从小鼠长基因间非编码RNA （lncRNA）位点列表中选择了四个高度保守和脑表达的转录本，这些转录本通常在其假定的启动子区域和跨外显子-内含子边界显示出明显的进化约束。我们在鸟类（鸡）、有袋动物（负鼠）和真兽哺乳动物（老鼠）中发现了一些最早的lncRNA同源物，并研究它们是否表现出大脑表达的保守性。与传统的蛋白质编码基因相比，这些非编码基因的序列、转录起始位点、外显子结构和长度都是高度可变的。如果lncrna仅限于密切相关的门，其生物学相关性将受到高度质疑。相反，它们在不同羊膜动物中的保存，它们在外显子结构上的明显保存，以及它们在胚胎和出生后早期大脑表达模式的相似性表明，它们是功能性RNA分子，其中一些在脊椎动物大脑发育中起作用。
Long considered to be the building block of life, it is now apparent that protein is only one of many functional products generated by the eukaryotic genome. Indeed, more of the human genome is transcribed into noncoding sequence than into protein-coding sequence. Nevertheless, whilst we have developed a deep understanding of the relationships between evolutionary constraint and function for protein-coding sequence, little is known about these relationships for non-coding transcribed sequence. This dearth of information is partially attributable to a lack of established non-protein-coding RNA (ncRNA) orthologs among birds and mammals within sequence and expression databases. Here, we performed a multi-disciplinary study of four highly conserved and brain-expressed transcripts selected from a list of mouse long intergenic noncoding RNA (lncRNA) loci that generally show pronounced evolutionary constraint within their putative promoter regions and across exon-intron boundaries. We identify some of the first lncRNA orthologs present in birds (chicken), marsupial (opossum), and eutherian mammals (mouse), and investigate whether they exhibit conservation of brain expression. In contrast to conventional protein-coding genes, the sequences, transcriptional start sites, exon structures, and lengths for these non-coding genes are all highly variable. The biological relevance of lncRNAs would be highly questionable if they were limited to closely related phyla. Instead, their preservation across diverse amniotes, their apparent conservation in exon structure, and similarities in their pattern of brain expression during embryonic and early postnatal stages together indicate that these are functional RNA molecules, of which some have roles in vertebrate brain development.
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影响因子：
56.9
作者：
Cheng, J;Kapranov, P;Gingeras, TR
通讯作者：
Gingeras, TR
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：
2.6
作者：
Bertone, P;Gerstein, M;Snyder, M
通讯作者：
Snyder, M
影响因子：
56.9
作者：
Duret, L;Chureau, C;Avner, P
通讯作者：
Avner, P
人类和小鼠基因组中的复杂基因座。
影响因子：
4.5
作者：
Engstrom, Par G.;Suzuki, Harukazu;Ninomiya, Noriko;Akalin, Altuna;Sessa, Luca;Lavorgna, Giovanni;Brozzi, Alessandro;Luzi, Lucilla;Tan, Sin Lam;Yang, Liang;Kunarso, Galih;ng, Edwin Lian-Cho Ng;Batalov, Serge;Wahlestedt, Claes;Kai, Chikatoshi;Kawai, Jun;Carninci, Piero;Hayashizaki, Yoshihide;Wells, Christine;Bajic, Vladimir B.;Orlando, Valerio;Reid, James F.;Lenhard, Boris;Lipovich, Leonard
通讯作者：
Lipovich, Leonard