ArticleNucleic acids research2015
Splicing factor SRSF1 negatively regulates alternative splicing of MDM2 under damage.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 65 citations in OpenAlex.
- Isoforms in action: The impact of transcript diversity in phenotype.Genetics and molecular biology · 2026Article
- The PIWI-interacting RNA CRAPIR alleviates myocardial ischemia‒reperfusion injury by reducing p53-mediated apoptosis via binding to SRSF1.Acta pharmacologica Sinica · 2025Article
- SRSF1-mediated alternative splicing regulates bladder cancer progression and cisplatin sensitivity through HIF1A/BNIP3/mitophagy axis.Journal of translational medicine · 2025Article
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- SRSF1 Is Required for Mitochondrial Homeostasis and Thermogenic Function in Brown Adipocytes Through its Control of Ndufs3 Splicing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A patient-derived organoid-based study identified an ASO targeting SNORD14E for endometrial cancer through reducing aberrant FOXM1 Expression and β-catenin nuclear accumulation.Journal of experimental & clinical cancer research : CR · 2023Article
- Towards understandings of serine/arginine-rich splicing factors.Acta pharmaceutica Sinica. B · 2023Review
- How Driver Oncogenes Shape and Are Shaped by Alternative Splicing Mechanisms in Tumors.Cancers · 2023Review
- Distinct H3K27me3 and H3K27ac Modifications in Neural Tube Defects Induced by Benzo[a]pyrene.Brain sciences · 2023Article
- Alternative RNA splicing defects in pediatric cancers: new insights in tumorigenesis and potential therapeutic vulnerabilities.Annals of oncology : official journal of the European Society for Medical Oncology · 2022Review
- SF3B1 inhibition disrupts malignancy and prolongs survival in glioblastoma patients through BCL2L1 splicing and mTOR/ß-catenin pathways imbalances.Journal of experimental & clinical cancer research : CR · 2022Article
- USP15 and USP4 facilitate lung cancer cell proliferation by regulating the alternative splicing of SRSF1.Cell death discovery · 2022Article
- Coordination of RNA Processing Regulation by Signal Transduction Pathways.Biomolecules · 2021Review
- Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1.Journal of experimental & clinical cancer research : CR · 2021Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- SRSF2 Regulation ofMolecular cancer research : MCR · 2020Article
- Genome-wide profiling of prognosis-related alternative splicing signatures in sarcoma.Annals of translational medicine · 2019Article
- Function, clinical application, and strategies of Pre-mRNA splicing in cancer.Cell death and differentiation · 2019Review
- Alternative Splicing in Angiogenesis.International journal of molecular sciences · 2019Review
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Genotoxic stress induces alternative splicing of the oncogene MDM2 generating MDM2-ALT1, an isoform attributed with tumorigenic properties. However, the mechanisms underlying this event remain unclear. Here we explore MDM2 splicing regulation by utilizing a novel minigene that mimics endogenous MDM2 splicing in response to UV and cisplatinum-induced DNA damage. We report that exon 11 is necessary and sufficient for the damage-specific alternative splicing of the MDM2 minigene and that the splicing factor SRSF1 binds exon 11 at evolutionarily conserved sites. Interestingly, mutations disrupting this interaction proved sufficient to abolish the stress-induced alternative splicing of the MDM2 minigene. Furthermore, SRSF1 overexpression promoted exclusion of exon 11, while its siRNA-mediated knockdown prevented the stress-induced alternative splicing of endogenous MDM2. Additionally, we observed elevated SRSF1 levels under stress and in tumors correlating with the expression of MDM2-ALT1. Notably, we demonstrate that MDM2-ALT1 splicing can be blocked by targeting SRSF1 sites on exon 11 using antisense oligonucleotides. These results present conclusive evidence supporting a negative role for SRSF1 in MDM2 alternative splicing. Importantly, we define for the first time, a clear-cut mechanism for the regulation of damage-induced MDM2 splicing and present potential strategies for manipulating MDM2 expression via splicing modulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.