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

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ingrid Ehrmann ◽  
James H Crichton ◽  
Matthew R Gazzara ◽  
Katherine James ◽  
Yilei Liu ◽  
...  

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.

2018 ◽  
Author(s):  
Ingrid Ehrmann ◽  
James H Crichton ◽  
Matthew R Gazzara ◽  
Katherine James ◽  
Yilei Liu ◽  
...  

2007 ◽  
Vol 176 (7) ◽  
pp. 929-939 ◽  
Author(s):  
Maria Paola Paronetto ◽  
Tilman Achsel ◽  
Autumn Massiello ◽  
Charles E. Chalfant ◽  
Claudio Sette

The RNA-binding protein Sam68 is involved in apoptosis, but its cellular mRNA targets and its mechanism of action remain unknown. We demonstrate that Sam68 binds the mRNA for Bcl-x and affects its alternative splicing. Depletion of Sam68 by RNA interference caused accumulation of antiapoptotic Bcl-x(L), whereas its up-regulation increased the levels of proapoptotic Bcl-x(s). Tyrosine phosphorylation of Sam68 by Fyn inverted this effect and favored the Bcl-x(L) splice site selection. A point mutation in the RNA-binding domain of Sam68 influenced its splicing activity and subnuclear localization. Moreover, coexpression of ASF/SF2 with Sam68, or fusion with an RS domain, counteracted Sam68 splicing activity toward Bcl-x. Finally, Sam68 interacted with heterogenous nuclear RNP (hnRNP) A1, and depletion of hnRNP A1 or mutations that impair this interaction attenuated Bcl-x(s) splicing. Our results indicate that Sam68 plays a role in the regulation of Bcl-x alternative splicing and that tyrosine phosphorylation of Sam68 by Src-like kinases can switch its role from proapoptotic to antiapoptotic in live cells.


2011 ◽  
Vol 59 (3) ◽  
pp. 452-459 ◽  
Author(s):  
Debin Xue ◽  
Yan Peng ◽  
Fenghua Wang ◽  
Robert W Allan ◽  
Dengfeng Cao

2000 ◽  
Vol 20 (17) ◽  
pp. 6287-6299 ◽  
Author(s):  
Fabienne Del Gatto-Konczak ◽  
Cyril F. Bourgeois ◽  
Caroline Le Guiner ◽  
Liliane Kister ◽  
Marie-Claude Gesnel ◽  
...  

2008 ◽  
Vol 17 (18) ◽  
pp. 2803-2818 ◽  
Author(s):  
Ingrid Ehrmann ◽  
Caroline Dalgliesh ◽  
Aikaterini Tsaousi ◽  
Maria Paola Paronetto ◽  
Bettina Heinrich ◽  
...  

2010 ◽  
Vol 24 (2) ◽  
pp. 288-296 ◽  
Author(s):  
Dengfeng Cao ◽  
Aijun Liu ◽  
Fenghua Wang ◽  
Robert W Allan ◽  
Kaiyong Mei ◽  
...  

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e26948 ◽  
Author(s):  
Daw-Jen Tsuei ◽  
Po-Huang Lee ◽  
Hsiao-Yu Peng ◽  
Shau-Lin Lu ◽  
De-Shiuan Su ◽  
...  

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