The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x
Open accessAbstract
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.
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Cites
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Signal-dependent regulation of splicing via phosphorylation of Sam68
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Cited by
A large-scale binding and functional map of human RNA-binding proteins
Van Nostrand, E. L., Freese, P., Pratt, G. A., Wang, X., Wei, X., Xiao, R., Blue, S. M., Chen, J.-Y., Cody, N. A. L., Dominguez, D., et al. (2020) · Nature · doi:10.1038/s41586-020-2077-3 · Cited by 1,317
Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches
Chen, M., & Manley, J. L. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2777 · Cited by 1,284
RNA-Binding Proteins in Cancer: Old Players and New Actors
Pereira, B., Billaud, M., & Almeida, R. (2017) · Trends in Cancer · doi:10.1016/j.trecan.2017.05.003 · Cited by 773
RNA splicing dysregulation and the hallmarks of cancer
Bradley, R. K., & Anczuków, O. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00541-7 · Cited by 579
Urbanski, L. M., Leclair, N., & Anczuków, O. (2018) · WIREs RNA · doi:10.1002/wrna.1476 · Cited by 389
Metadata
- Authors
- Paronetto, M. P., Achsel, T., Massiello, A., Chalfant, C. E., & Sette, C.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2007-03-19
- Volume
- 176
- Issue
- 7
- Pages
- 929-939
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2155432224
- Cited by
- 334
- References
- 38
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- green
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- Paronetto, M. P., Achsel, T., Massiello, A., Chalfant, C. E., & Sette, C. (2007). The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200701005
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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