Publication in detail

Elife. 2019 Jan 24;8. pii: e39304. doi: 10.7554/eLife.39304.

An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning.

Ehrmann, I; Crichton, JH; Gazzara, MR; James, K; Liu, Y; Grellscheid, SN; Curk, T; de Rooij, D; Steyn, JS; Cockell, S; Adams, IR; Barash, Y; Elliott, DJ

Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom. MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States. Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States. Life Sciences, Natural History Museum, London, United Kingdom. Department of Plant and Microbial Biology, University of Zürich, Zürich, Switzerland. School of Biological and Biomedical Sciences, University of Durham, Durham, United Kingdom. Laboratory of Bioinformatics, Faculty of Computer and Information Sciences, University of Ljubljana, Ljubljana, Slovenia. Reproductive Biology Group, Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands. Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Bioinformatics Support Unit, Faculty of Medical Sciences, Newcastle University, Newcastle, United Kingdom. Department of Computer and Information Science, University of Pennsylvania, Philadelphia, United States.

Abstract:
Male germ cells of all placental mammals express an ancient nuclear RNA binding protein of unknown function called RBMXL2. Here we find that deletion of the retrogene encoding RBMXL2 blocks spermatogenesis. Transcriptome analyses of age-matched deletion mice show that RBMXL2 controls splicing patterns during meiosis. In particular, RBMXL2 represses the selection of aberrant splice sites and the insertion of cryptic and premature terminal exons. Our data suggest a Rbmxl2 retrogene has been conserved across mammals as part of a splicing control mechanism that is fundamentally important to germ cell biology. We propose that this mechanism is essential to meiosis because it buffers the high ambient concentrations of splicing activators, thereby preventing poisoning of key transcripts and disruption to gene expression by aberrant splice site selection.

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