1. Mobilization of LINE-1 retrotransposons is restricted by Tex19.1 in mouse embryonic stem cells.
- Author
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MacLennan M, García-Cañadas M, Reichmann J, Khazina E, Wagner G, Playfoot CJ, Salvador-Palomeque C, Mann AR, Peressini P, Sanchez L, Dobie K, Read D, Hung CC, Eskeland R, Meehan RR, Weichenrieder O, García-Pérez JL, and Adams IR
- Subjects
- Animals, Gene Knockout Techniques, Mice, Nuclear Proteins genetics, Protein Binding, Proteolysis, Ubiquitin-Protein Ligases metabolism, Ubiquitination, Long Interspersed Nucleotide Elements, Mouse Embryonic Stem Cells physiology, Nuclear Proteins metabolism, RNA-Binding Proteins metabolism, Recombination, Genetic
- Abstract
Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization. We also show that TEX19.1 likely acts, at least in part, through promoting the activity of the E3 ubiquitin ligase UBR2 towards L1-ORF1p. Moreover, loss of Tex19.1 increases L1-ORF1p levels and L1 mobilization in pluripotent mouse embryonic stem cells, implying that Tex19.1 prevents de novo retrotransposition in the pluripotent phase of the germline cycle. These data show that post-translational regulation of L1 retrotransposons plays a key role in maintaining trans-generational genome stability in mammals.
- Published
- 2017
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