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SRSF10 Connects DNA Damage to the Alternative Splicing of Transcripts Encoding Apoptosis, Cell-Cycle Control, and DNA Repair Factors
- Source :
- Cell Reports; November 2016, Vol. 17 Issue: 8 p1990-2003, 14p
- Publication Year :
- 2016
-
Abstract
- RNA binding proteins and signaling components control the production of pro-death and pro-survival splice variants of Bcl-x. DNA damage promoted by oxaliplatin increases the level of pro-apoptotic Bcl-xS in an ATM/CHK2-dependent manner, but how this shift is enforced is not known. Here, we show that in normally growing cells, when the 5′ splice site of Bcl-xS is largely repressed, SRSF10 partially relieves repression and interacts with repressor hnRNP K and stimulatory hnRNP F/H proteins. Oxaliplatin abrogates the interaction of SRSF10 with hnRNP F/H and decreases the association of SRSF10 and hnRNP K with the Bcl-xpre-mRNA. Dephosphorylation of SRSF10 is linked with these changes. A broader analysis reveals that DNA damage co-opts SRSF10 to control splicing decisions in transcripts encoding components involved in DNA repair, cell-cycle control, and apoptosis. DNA damage therefore alters the interactions between splicing regulators to elicit a splicing response that determines cell fate.
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 17
- Issue :
- 8
- Database :
- Supplemental Index
- Journal :
- Cell Reports
- Publication Type :
- Periodical
- Accession number :
- ejs43398637
- Full Text :
- https://doi.org/10.1016/j.celrep.2016.10.071