The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression.

The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression.
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DOI:
10.1101/gr.132159.111
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发表时间:
2012-09
期刊:
影响因子:
7
通讯作者:
Guigó R
Guigó R
中科院分区:
生物学1区
文献类型:
--
作者:
Derrien T;Johnson R;Bussotti G;Tanzer A;Djebali S;Tilgner H;Guernec G;Martin D;Merkel A;Knowles DG;Lagarde J;Veeravalli L;Ruan X;Ruan Y;Lassmann T;Carninci P;Brown JB;Lipovich L;Gonzalez JM;Thomas M;Davis CA;Shiekhattar R;Gingeras TR;Hubbard TJ;Notredame C;Harrow J;Guigó R

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人类基因组包含成千上万的长链非编码rna (lncrna)。虽然一些研究已经证明了个体例子中引人注目的生物学和疾病作用,但由于缺乏全面的lncRNA注释,研究这些基因的分析和实验方法受到阻碍。在这里,我们展示并分析了迄今为止最完整的人类lncRNA注释,由ENCODE项目框架内的GENCODE联盟制作,包括9277个手工注释的基因,产生14,880个转录本。我们的分析表明,lncrna是通过与蛋白质编码基因相似的途径产生的,具有相似的组蛋白修饰谱、剪接信号和外显子/内含子长度。然而,与蛋白质编码基因相反,lncRNAs显示出惊人的双外显子转录本,它们主要定位于染色质和细胞核,并且一部分似乎优先被加工成小rna。与中性进化序列相比,它们承受着更强的选择压力——尤其是在启动子区域,启动子区域显示出与蛋白质编码基因相当的选择水平。重要的是,大约三分之一似乎是在灵长类谱系中出现的。综合分析其在人体多个器官和大脑区域的表达情况发现,lncRNAs的表达水平普遍低于蛋白质编码基因,且表现出更多的组织特异性表达模式,其中在大脑中表达的组织特异性lncRNAs占很大比例。表达相关性分析表明,lncRNAs与反义编码基因的表达呈显著正相关。这一GENCODE注释为未来lncrna的研究提供了宝贵的资源。
The human genome contains many thousands of long noncoding RNAs (lncRNAs). While several studies have demonstrated compelling biological and disease roles for individual examples, analytical and experimental approaches to investigate these genes have been hampered by the lack of comprehensive lncRNA annotation. Here, we present and analyze the most complete human lncRNA annotation to date, produced by the GENCODE consortium within the framework of the ENCODE project and comprising 9277 manually annotated genes producing 14,880 transcripts. Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths. In contrast to protein-coding genes, however, lncRNAs display a striking bias toward two-exon transcripts, they are predominantly localized in the chromatin and nucleus, and a fraction appear to be preferentially processed into small RNAs. They are under stronger selective pressure than neutrally evolving sequences—particularly in their promoter regions, which display levels of selection comparable to protein-coding genes. Importantly, about one-third seem to have arisen within the primate lineage. Comprehensive analysis of their expression in multiple human organs and brain regions shows that lncRNAs are generally lower expressed than protein-coding genes, and display more tissue-specific expression patterns, with a large fraction of tissue-specific lncRNAs expressed in the brain. Expression correlation analysis indicates that lncRNAs show particularly striking positive correlation with the expression of antisense coding genes. This GENCODE annotation represents a valuable resource for future studies of lncRNAs.
DOI: 10.1038/nature09906
发表时间: 2011-05-05
期刊: NATURE
影响因子: 64.8
作者:
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发表时间: 2012-09
期刊: Genome research
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DOI: 10.1126/science.1112014
发表时间: 2005-09-02
期刊: SCIENCE
影响因子: 56.9
作者:
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通讯作者: Hayashizaki, Y
DOI: 10.1371/journal.pcbi.1000176
发表时间: 2008-11
影响因子: 4.3
作者:
Dinger ME;Pang KC;Mercer TR;Mattick JS
通讯作者: Mattick JS
DOI: 10.1261/rna.2528811
发表时间: 2011-05-01
期刊: RNA
影响因子: 4.5
作者:
Askarian-Amiri, Marjan E.;Crawford, Joanna;Mattick, John S.
通讯作者: Mattick, John S.