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Letter

Analysis of 5' junctions of human LINE-1 and Alu retrotransposons suggests an alternative model for 5'-end attachment requiring microhomology-mediated end-joining

¹ Fachgebiet Pr2/Retroelemente, Paul-Ehrlich-Institut, D-63225 Langen, Germany ² Zentrum für Bioinformatik, Universität Hamburg, D-20146 Hamburg, Germany ³ Institut für Medizinische Biometrie und Epidemiologie, Universitätsklinikum Hamburg-Eppendorf, D-20246 Hamburg, Germany ⁴ Department of Human Genetics and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, 48105-0618, USA

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.

[Supplemental material is available online at www.genome.org and at http://www.zbh.uni-hamburg.de/research/GI/projects. php. The following individual kindly provided reagents, samples, or unpublished information as indicated in the paper: S.L. Martin.]

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.3421505. Freely available online through the Genome Research Immediate Open Access option.

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