scholarly journals The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x

2007 ◽  
Vol 176 (7) ◽  
pp. 929-939 ◽  
Author(s):  
Maria Paola Paronetto ◽  
Tilman Achsel ◽  
Autumn Massiello ◽  
Charles E. Chalfant ◽  
Claudio Sette
Keyword(s):  
Alternative Splicing ◽  
Tyrosine Phosphorylation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Live Cells ◽  
Hnrnp A1 ◽  
Splice Site Selection ◽  
Subnuclear Localization ◽  
Mrna Targets

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.

scholarly journals Region-specific alternative splicing in the nervous system: Implications for regulation by the RNA-binding protein NAPOR

RNA ◽  
2002 ◽  
Vol 8 (5) ◽  
pp. 671-685 ◽  
Author(s):  
WENQING ZHANG ◽  
HAIYING LIU ◽  
KYOUNGHA HAN ◽  
PAULA J. GRABOWSKI
Keyword(s):  
Nervous System ◽  
Alternative Splicing ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Specific Alternative

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
Keyword(s):  
Alternative Splicing ◽  
Dilated Cardiomyopathy ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals The RNA ‐binding protein Arrest (Bruno) regulates alternative splicing to enable myofibril maturation in Drosophila flight muscle

EMBO Reports ◽  
2014 ◽  
Vol 16 (2) ◽  
pp. 178-191 ◽  
Author(s):  
Maria L Spletter ◽  
Christiane Barz ◽  
Assa Yeroslaviz ◽  
Cornelia Schönbauer ◽  
Irene R S Ferreira ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Binding ◽  
Flight Muscle ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals The RNA-binding protein Rbfox2: an essential regulator of EMT-driven alternative splicing and a mediator of cellular invasion

Oncogene ◽  
2013 ◽  
Vol 33 (9) ◽  
pp. 1082-1092 ◽  
Author(s):  
C Braeutigam ◽  
L Rago ◽  
A Rolke ◽  
L Waldmeier ◽  
G Christofori ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cellular Invasion

scholarly journals Targeting of RBM10 to S1-1 Nuclear Bodies: Targeting Sequences and its Biological Significance

2019 ◽  
Author(s):  
Ling-Yu Wang ◽  
Sheng-Jun Xiao ◽  
Hiroyuki Kunimoto ◽  
Kazuaki Tokunaga ◽  
Hirotada Kojima ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Transcriptional Activity ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Biological Significance ◽  
Nuclear Bodies ◽  
Transient Component ◽  
Cellular Transcription ◽  
Splicing Machinery

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.

scholarly journals Phosphoregulation provides specificity to biomolecular condensates in the cell cycle and cell polarity

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Therese M. Gerbich ◽  
Grace A. McLaughlin ◽  
Katelyn Cassidy ◽  
Scott Gerber ◽  
David Adalsteinsson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nucleic Acids ◽  
Cell Polarity ◽  
Filamentous Fungus ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Ashbya Gossypii ◽  
Mrna Targets ◽  
Functional Identities

Biomolecular condensation is a way of organizing cytosol in which proteins and nucleic acids coassemble into compartments. In the multinucleate filamentous fungus Ashbya gossypii, the RNA-binding protein Whi3 regulates the cell cycle and cell polarity through forming macromolecular structures that behave like condensates. Whi3 has distinct spatial localizations and mRNA targets, making it a powerful model for how, when, and where specific identities are established for condensates. We identified residues on Whi3 that are differentially phosphorylated under specific conditions and generated mutants that ablate this regulation. This yielded separation of function alleles that were functional for either cell polarity or nuclear cycling but not both. This study shows that phosphorylation of individual residues on molecules in biomolecular condensates can provide specificity that gives rise to distinct functional identities in the same cell.

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