SRSF1 coordinates transcription and alternative splicing to modulate p53 and genome-maintenance
Abstract
Serine/arginine-rich splicing factor 1 (SRSF1) regulates alternative splicing and acts as a proto-oncogene, but its role in transcription remains poorly defined. We combined time-course RNA-seq with experimental validation to define SRSF1-dependent transcriptional and splicing programs. We validated 67 of 143 alternative-splicing events selected for experimental analysis. Among these, 44 were not annotated in GENCODE, including 15 containing previously unannotated exons. Thirty-five events showed concordant regulation in HEK293 and breast and prostate cancer cell lines, and 17 events in 16 genes affected p53 regulation or p53-dependent functions. SRSF1 overexpression reduced total p53, increased basal Ser15 phosphorylation, and increased apoptosis under basal and cisplatin-treated conditions but not following doxorubicin treatment. SRSF1 also increased transcription of 28 genes, 18 of which showed concordant regulation across the same cellular models. Mechanistic studies linked SRSF1-dependent transcriptional activation to P-TEFb mobilization from the 7SK snRNP, which controls P-TEFb availability for RNA polymerase II elongation. These findings identify distinct but concurrent SRSF1-regulated programs: transcriptional activation of genes associated with cellular signaling and organization and alternative splicing modulating genome-maintenance and p53-regulatory genes.
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BibTeX
@misc{paz2026srsf1,
title = {{SRSF1 coordinates transcription and alternative splicing to modulate p53 and genome-maintenance}},
author = {Sean Paz and Elena Bisotto and Massimo Caputi},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.759576},
url = {https://www.biorxiv.org/content/10.64898/2026.10.16.759576v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - SRSF1 coordinates transcription and alternative splicing to modulate p53 and genome-maintenance
AU - Sean Paz
AU - Elena Bisotto
AU - Massimo Caputi
PY - 2026
DA - 2026/10/16
PB - bioRxiv
DO - 10.64898/2026.10.16.759576
UR - https://www.biorxiv.org/content/10.64898/2026.10.16.759576v1
AB - Serine/arginine-rich splicing factor 1 (SRSF1) regulates alternative splicing and acts as a proto-oncogene, but its role in transcription remains poorly defined. We combined time-course RNA-seq with experimental validation to define SRSF1-dependent transcriptional and splicing programs. We validated 67 of 143 alternative-splicing events selected for experimental analysis. Among these, 44 were not annotated in GENCODE, including 15 containing previously unannotated exons. Thirty-five events showed concordant regulation in HEK293 and breast and prostate cancer cell lines, and 17 events in 16 genes affected p53 regulation or p53-dependent functions. SRSF1 overexpression reduced total p53, increased basal Ser15 phosphorylation, and increased apoptosis under basal and cisplatin-treated conditions but not following doxorubicin treatment. SRSF1 also increased transcription of 28 genes, 18 of which showed concordant regulation across the same cellular models. Mechanistic studies linked SRSF1-dependent transcriptional activation to P-TEFb mobilization from the 7SK snRNP, which controls P-TEFb availability for RNA polymerase II elongation. These findings identify distinct but concurrent SRSF1-regulated programs: transcriptional activation of genes associated with cellular signaling and organization and alternative splicing modulating genome-maintenance and p53-regulatory genes.
SN - 2692-8205
ER -