Somatic expression of LINE-1 elements in human tissues
Open accessAbstract
LINE-1 expression damages host DNA via insertions and endonuclease-dependent DNA double-strand breaks (DSBs) that are highly toxic and mutagenic. The predominant tissue of LINE-1 expression has been considered to be the germ line. We show that both full-length and processed L1 transcripts are widespread in human somatic tissues and transformed cells, with significant variation in both L1 expression and L1 mRNA processing. This is the first demonstration that RNA processing is a major regulator of L1 activity. Many tissues also produce translatable spliced transcript (SpORF2). An Alu retrotransposition assay, COMET assays and 53BP1 foci staining show that the SpORF2 product can support functional ORF2 protein expression and can induce DNA damage in normal cells. Tests of the senescence-associated beta-galactosidase expression suggest that expression of exogenous full-length L1, or the SpORF2 mRNA alone in human fibroblasts and adult stem cells triggers a senescence-like phenotype, which is one of the reported responses to DNA damage. In contrast to previous assumptions that L1 expression is germ line specific, the increased spectrum of tissues exposed to L1-associated damage suggests a role for L1 as an endogenous mutagen in somatic tissues. These findings have potential consequences for the whole organism in the form of cancer and mammalian aging.
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Overexpression of exogenous full length L1 induces a senescence-like phenotype in human fibroblasts and adult stem cells.
“overexpression of exogenous full length L1 has been shown to induce a senescence-like phenotype in human fibroblasts and adult stem cells9.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [9]
Mechanisms that silence retrotransposons in somatic cells are not completely efficient and may deteriorate with age.
“evidence has begun to accumulate indicating that the mechanisms which silence retrotransposons in somatic cells are not completely efficient9 and may deteriorate with age10,11.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [9]
Mutations in genes encoding DNMT3A, TET2 and ASXL1 account for greater than 70% of cases of ARCH.
“Mutations in genes encoding DNMT3A, TET2 (Supplementary Table 1) and additional sex-combs like 1 (ASXL1), which regulate DNA and histone methylation, account for greater than 70% of cases of ARCH 76-78 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [78]
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- Authors
- Belancio, V. P., Roy-Engel, A. M., Pochampally, R. R., & Deininger, P.
- Affiliations
- Tulane University (US)
- Corresponding author
- Deininger, Prescott
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-03-09
- Volume
- 38
- Issue
- 12
- Pages
- 3909-3922
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC2896524
- OpenAlex
- W2055705164
- Cited by
- 238
- References
- 69
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 13 · 2023: 9 · 2022: 23 · 2021: 12 · 2020: 13 · 2019: 12 · 2018: 14 · 2017: 13 · 2016: 21 · 2015: 23 · 2014: 15 · 2013: 18 · 2012: 14
- FWCI
- 19.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Science Foundation (0346411)
- Ellison Medical Foundation
- Louisiana Board of Regents
- Tulane University
- National Institutes of Health
- National Institute on Aging (K01AG030074)
- National Institute of General Medical Sciences (R01GM45668, R01GM079709, R01GM045668)
- National Center for Research Resources (P20RR020152)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- LINE-1 retrotransposons, ORF2 protein, retrotransposition, DNA double-strand breaks, DNA damage, cellular senescence, endogenous mutagenesis, 53BP1 foci, transformed cells, adult stem cells, cancer, aging
- MeSH terms
- Adult, Animals, Cell Line, DNA Damage, Endonucleases, Fibroblasts, Humans, RNA-Directed DNA Polymerase, RNA Splicing, RNA, Messenger, Stem Cells, Cellular Senescence, Long Interspersed Nucleotide Elements, Alu Elements, Polyadenylation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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