Transposable Elements Are Major Contributors to the Origin, Diversification, and Regulation of Vertebrate Long Noncoding RNAs
Open accessAbstract
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.
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11 of the 24 de-repressed retrotransposons overlapping activated RT-promoters overlap with promoters of annotated lncRNAs.
“Notably, 11 of these elements overlapped with the promoters of annotated lncRNAs (Fig. 5a), consistent with the previous finding that LTRs are enriched in the transcription start sites (TSSs) of lncRNAs80.”
From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [80]
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- Authors
- Kapusta, A., Kronenberg, Z., Lynch, V. J., Zhuo, X., Ramsay, L., Bourque, G., Yandell, M., & Feschotte, C.
- Affiliations
- University of Utah (US)
- University of Chicago (US)
- McGill University and Génome Québec Innovation Centre (CA)
- Corresponding author
- Feschotte, Cédric
- ORCID
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-25
- Volume
- 9
- Issue
- 4
- Pages
- e1003470
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC3636048
- OpenAlex
- W2029868997
- Cited by
- 687
- References
- 115
- Citations by year
- 2026: 21 · 2025: 27 · 2024: 60 · 2023: 52 · 2022: 57 · 2021: 70 · 2020: 53 · 2019: 52 · 2018: 68 · 2017: 58 · 2016: 50 · 2015: 62 · 2014: 42 · 2013: 13
- FWCI
- 67.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- University of Chicago (cc-by)
- Funders
- National Science Foundation (1126998)
- National Institutes of Health
- Canadian Institutes of Health Research (115090_1)
- National Human Genome Research Institute (R01HG004694)
- National Institute of General Medical Sciences (T32GM007464, R01GM077582)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- transposable elements, long non-coding RNA, lncRNA evolution, lncRNA biogenesis, cis-regulation, open chromatin, RNA editing, secondary structure, transcription initiation, splicing, polyadenylation, human, mice, zebrafish
- MeSH terms
- Animals, DNA Transposable Elements, Exons, Humans, Introns, Vertebrates, RNA, Long Noncoding
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