---
title: "SRSF1 controls transcription and alternative splicing to alter p53 signaling and genome maintenance"
id: "biorxiv-4-srsf1-coordinates-transcription-and-alternative-splicing-to-modulate-p53-and"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-4-srsf1-coordinates-transcription-and-alternative-splicing-to-modulate-p53-and"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.16.759576v1?rss=1"
published_at: "2026-10-19T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# SRSF1 controls transcription and alternative splicing to alter p53 signaling and genome maintenance
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-4-srsf1-coordinates-transcription-and-alternative-splicing-to-modulate-p53-and
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.16.759576v1?rss=1)
- **Published At:** 2026-10-19T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study combined time-course **RNA-seq** with experimental validation to define SRSF1-dependent transcriptional and splicing programs. Short, repeated sampling captured dynamic RNA changes after SRSF1 perturbation. - Investigators validated 67 of 143 selected alternative-splicing events by experimental assays; the cohort included many previously unannotated outcomes. The authors reported 44 events absent from GENCODE annotations. - Among the unannotated events, 15 introduced previously undescribed exons. These novel exons expand the catalog of SRSF1-regulated splice isoforms. - Thirty-five splicing events displayed concordant regulation in HEK293 cells and in breast and prostate cancer cell lines, indicating cross-cell-type conservation for a subset of targets. - Seventeen splicing events, spanning 16 genes, were linked by the authors to **p53** regulation or to p53-dependent cellular functions; the study team highlighted these as genome-maintenance–relevant. - SRSF1 overexpression reduced total p53 protein levels while increasing basal phosphorylation at Ser15; the same manipulation increased apoptosis under basal conditions and after cisplatin exposure but did not increase apoptosis following doxorubicin. - On the transcription side, SRSF1 increased steady-state transcript levels of 28 genes; 18 of those genes showed concordant upregulation across the same panel of cellular models. - Mechanistic experiments implicated mobilization of **P-TEFb** from the **7SK snRNP** as the connection between SRSF1 and enhanced RNA polymerase II elongation and transcriptional activation, according to the authors. - The authors conclude there are distinct yet concurrent SRSF1-regulated programs: a transcriptional activation module affecting cellular signaling and organization, and an alternative-splicing module that modulates genome-maintenance and **p53**-regulatory genes. - This work is posted as a preprint on bioRxiv and has not been certified by peer review; the authors and readers should interpret findings accordingly.
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Sean Paz Florida Atlantic University, United States * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Sean%2BPaz%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Paz%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASean%2BPaz%2B) Elena Bisotto Florida Atlantic University, United States * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Elena%2BBisotto%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bisotto%20E&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AElena%2BBisotto%2B) Massimo Caputi Florida Atlantic University, United States * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Massimo%2BCaputi%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Caputi%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMassimo%2BCaputi%2B) * [ORCID record for Massimo Caputi](http://orcid.org/0000-0002-4926-9700 "Open in new tab") * For correspondence: mcaputi@health.fau.edu * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.16.759576v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5884456/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.16.759576v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5884456/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.16.759576v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5884456/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.16.759576v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5884456/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## 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. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC-ND 4.0 International license](http://creativecommons.org/licenses/by-nc-nd/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.16.759576v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/19/2026.10.16.759576.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) SRSF1 coordinates transcription and alternative splicing to modulate p53 and genome-maintenance Sean Paz, Elena Bisotto, Massimo Caputi bioRxiv 2026.10.16.759576; doi: https://doi.org/10.64898/2026.10.16.759576 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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