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

Ehrmann, Ingrid; Crichton, James H; Gazzara, Matthew R; James, Katherine; Liu, Yilei; Grellscheid, Sushma Nagaraja; Curk, Tomaž; de Rooij, Dirk; Steyn, Jannetta S; Cockell, Simon; Adams, Ian R; Barash, Yoseph; Elliott, David J

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


Authors

Ingrid Ehrmann

James H Crichton

Matthew R Gazzara

Katherine James

Yilei Liu

Tomaž Curk

Dirk de Rooij

Jannetta S Steyn

Simon Cockell

Ian R Adams

Yoseph Barash

David J Elliott



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.

Citation

Ehrmann, I., Crichton, J. H., Gazzara, M. R., James, K., Liu, Y., Grellscheid, S. N., …Elliott, D. J. (2019). An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning. eLife, 8, Article e39304. https://doi.org/10.7554/elife.39304

Journal Article Type Article
Acceptance Date Dec 18, 2018
Online Publication Date Jan 24, 2019
Publication Date Jan 24, 2019
Deposit Date Feb 1, 2019
Publicly Available Date Feb 1, 2019
Journal eLife
Publisher eLife Sciences Publications
Peer Reviewed Peer Reviewed
Volume 8
Article Number e39304
DOI https://doi.org/10.7554/elife.39304

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Published Journal Article (6.4 Mb)
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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright 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.





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