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PMID: 23637635 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs.

PLoS genetics ·Vol. 9 ·No. 4 ·2013-04-00 ·Pages e1003470

Kapusta A, Kronenberg Z, Lynch VJ, Zhuo X, Ramsay L, Bourque G, Yandell M, Feschotte C

Abstract

Advances in vertebrate genomics have uncovered thousands of loci encoding long noncoding RNAs (lncRNAs). While progress has been made in elucidating the regulatory functions of lncRNAs, little is known about their origins and evolution. Here we explore the contribution of transposable elements (TEs) to the makeup and regulation of lncRNAs in human, mouse, and zebrafish. Surprisingly, TEs occur in more than two thirds of mature lncRNA transcripts and account for a substantial portion of total lncRNA sequence (~30% in human), whereas they seldom occur in protein-coding transcripts. While TEs contribute less to lncRNA exons than expected, several TE families are strongly enriched in lncRNAs. There is also substantial interspecific variation in the coverage and types of TEs embedded in lncRNAs, partially reflecting differences in the TE landscapes of the genomes surveyed. In human, TE sequences in lncRNAs evolve under greater evolutionary constraint than their non-TE sequences, than their intronic TEs, or than random DNA. Consistent with functional constraint, we found that TEs contribute signals essential for the biogenesis of many lncRNAs, including ~30,000 unique sites for transcription initiation, splicing, or polyadenylation in human. In addition, we identified ~35,000 TEs marked as open chromatin located within 10 kb upstream of lncRNA genes. The density of these marks in one cell type correlate with elevated expression of the downstream lncRNA in the same cell type, suggesting that these TEs contribute to cis-regulation. These global trends are recapitulated in several lncRNAs with established functions. Finally a subset of TEs embedded in lncRNAs are subject to RNA editing and predicted to form secondary structures likely important for function. In conclusion, TEs are nearly ubiquitous in lncRNAs and have played an important role in the lineage-specific diversification of vertebrate lncRNA repertoires.

MeSH Terms
Animals DNA Transposable Elements Exons Humans Introns RNA, Long Noncoding/genetics Vertebrates/genetics
Chemicals
DNA Transposable Elements RNA, Long Noncoding
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kapusta Aurélie
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
Kronenberg Zev
Lynch Vincent J
Zhuo Xiaoyu
Ramsay LeeAnn
Bourque Guillaume
Yandell Mark
Feschotte Cédric
Conflict of Interest

The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1003470
Published
2013-04-00
Epub
2013-00-25
Pages
e1003470
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC3636048
Subset
IM
Grants
NHGRI NIH HHS · R01 HG004694 · United States
NIGMS NIH HHS · R01-GM077582 · United States
NIGMS NIH HHS · T32 GM007464 · United States
NHGRI NIH HHS · R01-HG004694 · United States
CIHR · MOP-115090 · Canada
NIGMS NIH HHS · R01 GM077582 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.1003470 PMC Full Text View journal details
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