RT Journal Article SR Electronic T1 Tex19.1 Restricts LINE-1 Mobilisation in Mouse Embryonic Stem Cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 102442 DO 10.1101/102442 A1 Marie MacLennan A1 Marta García-Cañadas A1 Judith Reichmann A1 Elena Khazina A1 Carmen Salvador-Palomeque A1 Abigail R. Mann A1 Paula Peressini A1 Laura Sanchez A1 Christopher J. Playfoot A1 David Read A1 Chao-Chun Hung A1 Ragnhild Eskeland A1 Richard R. Meehan A1 Oliver Weichenrieder A1 Jose Luis GarcíaPérez A1 Ian R. Adams YR 2017 UL http://biorxiv.org/content/early/2017/02/09/102442.abstract AB Mobilisation of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution. In humans, retrotransposon mobilisation is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilise 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 mobilisation. 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, we show that loss of Tex19.1 increases L1-ORF1p levels and mobilisation of L1 reporters in pluripotent mouse embryonic stem cells implying that Tex19.1 prevents new retrotransposition-mediated mutations from arising in the germline genome. These data show that post-translational regulation of L1 retrotransposons plays a key role in maintaining trans-generational genome stability in the epigenetically dynamic developing mammalian germline.