scholarly journals RNA binding protein 24 deletion disrupts global alternative splicing and causes dilated cardiomyopathy

2018 ◽  
Vol 10 (6) ◽  
pp. 405-416 ◽  
Author(s):  
Jing Liu ◽  
Xu Kong ◽  
Mengkai Zhang ◽  
Xiao Yang ◽  
Xiuqin Xu
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.


RNA ◽  
2002 ◽  
Vol 8 (5) ◽  
pp. 671-685 ◽  
Author(s):  
WENQING ZHANG ◽  
HAIYING LIU ◽  
KYOUNGHA HAN ◽  
PAULA J. GRABOWSKI

EMBO Reports ◽  
2014 ◽  
Vol 16 (2) ◽  
pp. 178-191 ◽  
Author(s):  
Maria L Spletter ◽  
Christiane Barz ◽  
Assa Yeroslaviz ◽  
Cornelia Schönbauer ◽  
Irene R S Ferreira ◽  
...  

Oncogene ◽  
2013 ◽  
Vol 33 (9) ◽  
pp. 1082-1092 ◽  
Author(s):  
C Braeutigam ◽  
L Rago ◽  
A Rolke ◽  
L Waldmeier ◽  
G Christofori ◽  
...  

2019 ◽  
Author(s):  
Ling-Yu Wang ◽  
Sheng-Jun Xiao ◽  
Hiroyuki Kunimoto ◽  
Kazuaki Tokunaga ◽  
Hirotada Kojima ◽  
...  

AbstractRBM10 is an RNA-binding protein that regulates alternative splicing (AS). This protein localizes to the extra-nucleolar nucleoplasm and S1-1 nuclear bodies (NBs). We investigated the biological significance of RBM10 localization to S1-1 NBs, which is poorly understood. Our analyses revealed that RBM10 possesses two S1-1 NB-targeting sequences (NBTSs), one in the KEKE motif region and another in the C2H2 Zn finger (ZnF). These NBTSs acted synergistically and were sufficient for localization of RBM10 to S1-1 NBs. Furthermore, the C2H2 ZnF not only acted as an NBTS, but was also essential for regulation of AS by RBM10. RBM10 did not participate in S1-1 NB formation. We confirmed the previous finding that localization of RBM10 to S1-1 NBs increases as cellular transcriptional activity decreases and vice versa. These results indicate that RBM10 is a transient component of S1-1 NBs and is sequestered in these structures via its NBTSs when cellular transcription decreases. We propose that the NB-targeting activity of the C2H2 ZnF is induced when it is not bound to pre-mRNA or the splicing machinery complex under conditions of reduced transcription.


2020 ◽  
Vol 66 (5) ◽  
pp. 459-467
Author(s):  
Manami SENOO ◽  
Hiroshi HOZOJI ◽  
Yu ISHIKAWA-YAMAUCHI ◽  
Takashi TAKIJIRI ◽  
Sho OHTA ◽  
...  

2019 ◽  
Vol 40 (4) ◽  
pp. 153-161 ◽  
Author(s):  
Yuuki HORII ◽  
Takahiko SHIINA ◽  
Saki UEHARA ◽  
Kanako NOMURA ◽  
Hiroki SHIMAOKA ◽  
...  

2019 ◽  
Vol 132 (16) ◽  
pp. jcs230276 ◽  
Author(s):  
Rachel Caines ◽  
Amy Cochrane ◽  
Sophia Kelaini ◽  
Marta Vila-Gonzalez ◽  
Chunbo Yang ◽  
...  

2007 ◽  
Vol 26 (6) ◽  
pp. 1670-1680 ◽  
Author(s):  
Diana Bellavia ◽  
Marco Mecarozzi ◽  
Antonio F Campese ◽  
Paola Grazioli ◽  
Claudio Talora ◽  
...  

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