An Ancient Germ Cell-specific RNA-binding Protein Protects the Germline from Cryptic Splice Site Poisoning

Overview

Journal Elife

Specialty Biology

Date 2019 Jan 25

PMID 30674417

Citations 22

Authors

Ingrid Ehrmann

James H Crichton

Matthew R Gazzara

Katherine James

Yilei Liu

Sushma Nagaraja Grellscheid

Tomaz Curk

Dirk de Rooij

Jannetta S Steyn

Simon Cockell

Ian R Adams

Yoseph Barash

David J Elliott

Affiliations

Soon will be listed here.

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 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.

Citing Articles

An ultra-conserved poison exon in the Tra2b gene encoding a splicing activator is essential for male fertility and meiotic cell division.

Dalgliesh C, Aldalaqan S, Atallah C, Best A, Scott E, Ehrmann I EMBO J. 2025; 44(3):877-902.

PMID: 39748121 PMC: 11791180. DOI: 10.1038/s44318-024-00344-6.

The Intricate Functional Networks of Pre-mRNA Alternative Splicing in Mammalian Spermatogenesis.

Jiang N, Li Y, Yin L, Yuan S, Wang F Int J Mol Sci. 2024; 25(22).

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Altered mRNA transport and local translation in iNeurons with RNA binding protein knockdown.

Dargan R, Mikheenko A, Johnson N, Packer B, Li Z, Craig E bioRxiv. 2024; .

PMID: 39386562 PMC: 11463369. DOI: 10.1101/2024.09.26.615153.

An anciently diverged family of RNA binding proteins maintain correct splicing of a class of ultra-long exons through cryptic splice site repression.

Siachisumo C, Luzzi S, Aldalaqan S, Hysenaj G, Dalgliesh C, Cheung K Elife. 2024; 12.

PMID: 39356106 PMC: 11446547. DOI: 10.7554/eLife.89705.

hnRNPs: roles in neurodevelopment and implication for brain disorders.

Tilliole P, Fix S, Godin J Front Mol Neurosci. 2024; 17:1411639.

PMID: 39086926 PMC: 11288931. DOI: 10.3389/fnmol.2024.1411639.

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