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Comparative Transcriptomics Analyses across Species, Organs, and Developmental Stages Reveal Functionally Constrained lncRNAs

Journal Article · · Molecular Biology and Evolution
 [1];  [2]
  1. École Polytechnique Fédérale de Lausanne (EPFL), Lausanne (Switzerland); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. École Polytechnique Fédérale de Lausanne (EPFL), Lausanne (Switzerland); Univ. de Lyon, Villeurbanne (France)
The functionality of long noncoding RNAs (lncRNAs) is disputed. In general, lncRNAs are under weak selective pressures, suggesting that the majority of lncRNAs may be nonfunctional. However, although some surveys showed negligible phenotypic effects upon lncRNA perturbation, key biological roles were demonstrated for individual lncRNAs. Most lncRNAs with proven functions were implicated in gene expression regulation, in pathways related to cellular pluripotency, differentiation, and organ morphogenesis, suggesting that functional lncRNAs may be more abundant in embryonic development, rather than in adult organs. To test this hypothesis, we perform a multidimensional comparative transcriptomics analysis, across five developmental time points (two embryonic stages, newborn, adult, and aged individuals), four organs (brain, kidney, liver, and testes), and three species (mouse, rat, and chicken). We find that, overwhelmingly, lncRNAs are preferentially expressed in adult and aged testes, consistent with the presence of permissive transcription during spermatogenesis. LncRNAs are often differentially expressed among developmental stages and are less abundant in embryos and newborns compared with adult individuals, in agreement with a requirement for tighter expression control and less tolerance for noisy transcription early in development. For differentially expressed lncRNAs, we find that the patterns of expression variation among developmental stages are generally conserved between mouse and rat. Moreover, lncRNAs expressed above noise levels in somatic organs and during development show higher evolutionary conservation, in particular, at their promoter regions. Thus, we show that functionally constrained lncRNA loci are enriched in developing organs, and we suggest that many of these loci may function in an RNA-independent manner.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
Agence Nationale pour la Recherche; Swiss NAtinoal Science Foundation; USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1603589
Journal Information:
Molecular Biology and Evolution, Journal Name: Molecular Biology and Evolution Journal Issue: 1 Vol. 37; ISSN 0737-4038
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

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