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

Ehrmann, Ingrid and Crichton, James H. and Gazzara, Matthew R. and James, Katherine and Liu, Yilei and Grellscheid, Sushma Nagaraja and Curk, Tomaž and de Rooij, Dirk and Steyn, Jannetta S. and Cockell, Simon and Adams, Ian R. and Barash, Yoseph and Elliott, David J. (2019) 'An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning.', eLife., 8 . e39304.


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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Publisher statement:© Copyright Ehrmann et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Date accepted:18 December 2018
Date deposited:01 February 2019
Date of first online publication:24 January 2019
Date first made open access:01 February 2019

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