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Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals.

ABSTRACT: Long intergenic noncoding RNAs (lincRNAs) play diverse regulatory roles in human development and disease, but little is known about their evolutionary history and constraint. Here, we characterize human lincRNA expression patterns in nine tissues across six mammalian species and multiple individuals. Of the 1898 human lincRNAs expressed in these tissues, we find orthologous transcripts for 80% in chimpanzee, 63% in rhesus, 39% in cow, 38% in mouse, and 35% in rat. Mammalian-expressed lincRNAs show remarkably strong conservation of tissue specificity, suggesting that it is selectively maintained. In contrast, abundant splice-site turnover suggests that exact splice sites are not critical. Relative to evolutionarily young lincRNAs, mammalian-expressed lincRNAs show higher primary sequence conservation in their promoters and exons, increased proximity to protein-coding genes enriched for tissue-specific functions, fewer repeat elements, and more frequent single-exon transcripts. Remarkably, we find that ?20% of human lincRNAs are not expressed beyond chimpanzee and are undetectable even in rhesus. These hominid-specific lincRNAs are more tissue specific, enriched for testis, and faster evolving within the human lineage.

SUBMITTER: Washietl S

PROVIDER: S-EPMC3975061 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals.

Washietl Stefan S Kellis Manolis M Garber Manuel M

Genome research 20140115 4

Long intergenic noncoding RNAs (lincRNAs) play diverse regulatory roles in human development and disease, but little is known about their evolutionary history and constraint. Here, we characterize human lincRNA expression patterns in nine tissues across six mammalian species and multiple individuals. Of the 1898 human lincRNAs expressed in these tissues, we find orthologous transcripts for 80% in chimpanzee, 63% in rhesus, 39% in cow, 38% in mouse, and 35% in rat. Mammalian-expressed lincRNAs sh ...[more]

PMID: 24429298

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Project description:Mouse and rats are staple model organisms that have been traditionally used for oncological studies; however, their short lifespan and highly prone to cancers limit their utilizationsin understanding the mechanisms of cancer resistance. In recent years, several studies of the non-standard long-lived mammalian species like naked mole rat (NMR) have provided new insights of mechanisms in natural anti-cancer. How long-lived species genetically maintain longevity and cancer-resistance remains largely elusive. To better understand the underlying anti-cancer mechanisms in long-lived mammals, we genome widely identified long noncoding RNA (lncRNA) transcripts of two longevous mammals, bowhead whale (BW, Balaena mysticetus) and Brandt's bat (BB, Myotis brandtii) and featured their sequence traits, expression patterns, and their correlations with cancer-resistance. Similar with naked mole rat (NMR, Heterocephalus glaber), the most long-lived rodent, BW and BB lncRNAs show low sequence conservation and dynamic expressions among tissues and physiological stages. By utilizing k-mers clustering, 75-136 of BW, BB and NMR lncRNAs were found in close relation (Pearson's r ≥0.9, p < 0.01) with human ageing diseases related lncRNAs (HAR-Lncs). In addition, we observed thousands of BB and BW lncRNAs strongly co-expressed (r > 0.8 or r <-0.8, p < 0.01) with potential tumour suppressors, indicating that lncRNAs are potentially involved in anti-cancer regulation in long-lived mammals. Our study provides the basis for lncRNA researches in perspectives of evolution and anti-cancer studies. Abbreviations: BW: bowhead whale; BB: Brandt's bat; NMR: naked mole rat; LLM: long-lived mammal; HTS: human tumour-suppressors; PTS: potential tumour suppressor; ARD: ageing related diseases; HAR-Lncs: lncRNAs that related with human ageing diseases; Kmer-lncs: lncRNAs in long-lived mammal species that corelated (Pearson'sr ≥0.9, p < 0.01) with the 10 HAR-Lncs by k-mers clustering; All-lncs: all the lncRNAs in long-lived mammal species; SDE-lncs: significant differentially expressed lncRNAs.

Dataset Information

Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals.

Publications

Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals.

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