ArticleGenes & development2020
Recurrent SRSF2 mutations in MDS affect both splicing and NMD.
Article in Genes & development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 83 citations in OpenAlex.
- Sensitivity to ATR-CHK1 pathway inhibition in MDS/AML is enhanced by SRSF2 mutations and reduced by RUNX1 loss.Leukemia · 2026Article
- TargetingGenes & development · 2026Article
- An antisense antidote to oncogenic poison exons.Genes & development · 2026Article
- The splicing factor hnRNPA1 promotes osimertinib resistance in lung adenocarcinoma by regulating NEDD4L alternative splicing.Oncogene · 2026Article
- Mechanisms of LARP7 in regulating the progression of non-small cell lung cancer.Journal of thoracic disease · 2026Article
- Nonsense-Mediated RNA Decay Is a Targetable Vulnerability in Splicing Factor Mutant Myeloid Neoplasms by Enhancing R-Loop Accumulation and DNA Damage.Cancer research · 2026Article
- Review
- Nonsense-mediated mRNA decay: friend or foe in cancer biology?Cell communication and signaling : CCS · 2026Review
- Repression of FOSL1 augments ferroptosis to overcome oxaliplatin resistance in colorectal cancer by acting on SRSF2.Molecular biology reports · 2026Article
- Pharmacological perturbation of splicing elicits SMG1 reduction: Implications for cancer therapy.iScience · 2026Article
- A Yeast-Based High-Throughput Screening Platform for the Discovery of Novel pre-mRNA Splicing Modulators.ACS chemical biology · 2026Article
- SRSF2 mutations drive daunorubicin resistance in acute myeloid leukemia via THBS1 stabilization.Journal of experimental & clinical cancer research : CR · 2026Article
- Synergistic intragenic epigenetic deregulation by IDH2 and SRSF2 mutations causes mis-splicing of key transcriptional regulators.Science advances · 2026Article
- Myelodysplastic syndrome progress to acute myeloid leukemia: new insights and updates.Frontiers in immunology · 2026Review
- Unlocking the undruggable spliceosome: generative AI and structural dynamics in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Nonsense-mediated mRNA decay: a key regulatory system engaged in cancer.Cell communication and signaling : CCS · 2025Review
- Oncogenic DEAD-box ATPase DDX41 establishes transcript ensembles via CLK3-dependent and -independent mechanisms.Nature communications · 2025Article
- A Yeast-Based High-Throughput Screening Platform for the Discovery of Novel pre-mRNA Splicing Modulators.bioRxiv : the preprint server for biology · 2025Article
- The role of ASXL1, SRSF2, and EZH2 mutations in chromatin dysregulation of myelodysplastic neoplasia and acute myeloid leukemia.Leukemia · 2025Review
- SRSF6 and SRSF1 coordinately enhance the inclusion of humanNAR molecular medicine · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Oncogenic mutations in the RNA splicing factors SRSF2, SF3B1, and U2AF1 are the most frequent class of mutations in myelodysplastic syndromes and are also common in clonal hematopoiesis, acute myeloid leukemia, chronic lymphocytic leukemia, and a variety of solid tumors. They cause genome-wide splicing alterations that affect important regulators of hematopoiesis. Several mRNA isoforms promoted by the various splicing factor mutants comprise a premature termination codon (PTC) and are therefore potential targets of nonsense-mediated mRNA decay (NMD). In light of the mechanistic relationship between splicing and NMD, we sought evidence for a specific role of mutant SRSF2 in NMD. We show that SRSF2 Pro95 hot spot mutations elicit enhanced mRNA decay, which is dependent on sequence-specific RNA binding and splicing. SRSF2 mutants enhance the deposition of exon junction complexes (EJCs) downstream from the PTC through RNA-mediated molecular interactions. This architecture then favors the association of key NMD factors to elicit mRNA decay. Gene-specific blocking of EJC deposition by antisense oligonucleotides circumvents aberrant NMD promoted by mutant SRSF2, restoring the expression of PTC-containing transcript. Our study uncovered critical effects of SRSF2 mutants in hematologic malignancies, reflecting the regulation at multiple levels of RNA metabolism, from splicing to decay.
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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.