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.
“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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Mobility Pathways for Vertebrate L1, L2, CR1, and RTE Clade Retrotransposons
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The Influence of LINE-1 and SINE Retrotransposons on Mammalian Genomes
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HPV 5 and 8 E6 expression reduces ATM protein levels and attenuates LINE-1 retrotransposition
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Discovery and characterization of Alu repeat sequences via precise local read assembly
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Novel retrotransposon analysis reveals multiple mobility pathways dictated by hostsPreprint
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Insertion of Retrotransposons at Chromosome Ends: Adaptive Response to Chromosome Maintenance
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LINE-Like Retrotransposition inSaccharomyces cerevisiae
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The Flow of the Gibbon LAVA Element Is Facilitated by the LINE-1 Retrotransposition Machinery
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Internal priming: An opportunistic pathway for L1 and Alu retrotransposition in hominins
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In and out: Evolution of viral sequences in the mitochondrial genomes of legumes (Fabaceae)
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Mechanism of Alu integration into the human genome
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Evolutionary modes of emergence of short interspersed nuclear element ( SINE ) families in grasses
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Human LINE-1 retrotransposons: impacts on the genome and regulation by host factors
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Completion of LINE integration involves an open ‘4-way’ branched DNA intermediate
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Modeling neutral evolution of Alu elements using a branching process
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mRNA Retrotransposition Coupled with 5' Inversion as a Possible Source of New Genes
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Discovery of short pseudogenes derived from messenger RNAs
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Heads or tails: L1 insertion-associated 5' homopolymeric sequences
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Discovery of a new repeat family in the Callithrix jacchus genomePreprint
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The 5′ truncation of retrotransposon L1: a process of genome integrity
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Genomic alterations upon integration of zebrafish L1 elements revealed by the TANT method
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Retrotransposon insertion as a novel mutational cause of spinal muscular atrophy
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Targeted insertion of large genetic payloads using cas directed LINE-1 reverse transcriptase
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Regulation of mammalian LINE1 retrotransposon transcription
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Synchronous L1 retrotransposition events promote chromosomal crossover early in human tumorigenesisPreprint
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Intragenic L1 Insertion: One Possibility of Brain Disorder
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Integrated mechanism for the generation of the 5′ junctions of LINE inserts
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Rejuvenation of piRNAs in emergence of cancer and other diseases
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LINE retrotransposition and host DNA repair machinery
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A comprehensive analysis of gorilla-specific LINE-1 retrotransposons
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Integrated mechanism for the generation of the 5′ junctions of LINE inserts
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2 Molecular Evidence on Primate Origins and Evolution
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Rétrotransposons et cellules somatiques
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- 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 › Agricultural and Biological Sciences › Plant Science › 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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