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Analysis of 5′ junctions of human LINE-1 and Alu retrotransposons suggests an alternative model for 5′-end attachment requiring microhomology-mediated end-joining
Open accessAbstract
Insertion of the human non-LTR retrotransposon LINE-1 (L1) into chromosomal DNA is thought to be initiated by a mechanism called target-primed reverse transcription (TPRT). This mechanism readily accounts for the attachment of the 3′-end of an L1 copy to the genomic target, but the subsequent integration steps leading to the attachment of the 5′-end to the chromosomal DNA are still cause for speculation. By applying bioinformatics to analyze the 5′ junctions of recent L1 insertions in the human genome, we provide evidence that L1 uses at least two distinct mechanisms to link the 5′-end of the nascent L1 copy to its genomic target. While 5′-truncated L1 elements show a statistically significant preference for short patches of overlapping nucleotides between their target site and the point of truncation, full-length insertions display no distinct bias for such microhomologies at their 5′-ends. In a second genome-wide approach, we analyzed Alu elements to examine whether these nonautonomous retrotransposons, which are thought to be mobilized through L1 proteins, show similar characteristics. We found that Alu elements appear to be predominantly integrated via a pathway not involving overlapping nucleotides. The results indicate that a cellular nonhomologous DNA end-joining pathway may resolve intermediates from incomplete L1 retrotransposition events and thus lead to 5′ truncations.
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“Computational analyses of de novo L1 integrations and genomic L1 integrations have shown that most integrations proceed through a microhomology process for priming L1 DNA synthesis.9”
From The Human LINE-1 Retrotransposon Creates DNA Double-strand Breaks (2006) · cites this paper as [9]
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Reverse Transcriptase Encoded by a Human Transposable Element
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Han, K. (2006) · Louisiana State University · doi:10.31390/gradschool_dissertations.807
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Sen, S. K. (2008) · Louisiana State University · doi:10.31390/gradschool_dissertations.1306
Hartig, N., Seibt, K. M., & Heitkam, T. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.04.512097
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Cellular factors controlling human L1 retrotransposition
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Co-option of retrotransposons promotes antibody diversification
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In vivo Gene Writing with engineered retrotransposons
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Metadata
- Authors
- Zingler, N., Willhoeft, U., Brose, H.-P., Schoder, V., Jahns, T., Hanschmann, K.-M. O., Morrish, T. A., Löwer, J., & Schumann, G. G.
- Affiliations
- Paul Ehrlich Institut (DE)
- Universität Hamburg (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- University of Michigan (US)
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-06
- Volume
- 15
- Issue
- 6
- Pages
- 780-789
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC1142468
- OpenAlex
- W2041586254
- Cited by
- 111
- References
- 59
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 7 · 2020: 1 · 2019: 4 · 2017: 3 · 2016: 7 · 2015: 8 · 2014: 8 · 2013: 3 · 2012: 2
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Genome Research (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- National Institute of General Medical Sciences (GM60518, R01GM060518)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- LINE-1 retrotransposons, Alu elements, microhomology-mediated end joining, non-homologous end joining, target-primed reverse transcription, retrotransposition
- MeSH terms
- Chromosomes, Human, DNA Replication, Humans, Models, Genetic, Recombination, Genetic, Sequence Homology, Nucleic Acid, Genome, Human, Mutagenesis, Insertional, Long Interspersed Nucleotide Elements, Alu Elements
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