ArticleProceedings of the National Academy of Sciences of the United States of America2015
Disease-associated mutation in SRSF2 misregulates splicing by altering RNA-binding affinities.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
163 citing papers in PubMed, 1 synthesis or guideline pooled it, 206 citations in OpenAlex.
- Alternative splicing and cancer: a systematic review.Signal transduction and targeted therapy · 2021Pooled it
- SRSF2 P95H induces monocytic priming of human hematopoietic stem and progenitor cells.Leukemia · 2026Article
- TargetingGenes & development · 2026Article
- Review
- Long-read cDNA sequencing reveals novel isoforms and spliceosome-mutant-enriched transcripts in AML and MDS.bioRxiv : the preprint server for biology · 2026Article
- Non-Enzymatic MGO-Glycation of SRSF2 Drives RNA Mis-Splicing.Journal of the American Chemical Society · 2026Article
- Article
- The human branchpoint-interacting stem-loop sequence and structure regulates U2 snRNA expression, branchpoint recognition, and the transcriptome.Nucleic acids research · 2026Article
- Inactivation ofLife (Basel, Switzerland) · 2026Article
- A Yeast-Based High-Throughput Screening Platform for the Discovery of Novel pre-mRNA Splicing Modulators.ACS chemical biology · 2026Article
- Vulnerability of SRSF2-mutated chronic myelomonocytic leukemia to perturbation of the cGAS-STING pathway.Blood advances · 2026Article
- Mitochondrial antioxidant enzyme (SOD2) at the crossroads of redox signaling and cancer progression.Free radical research · 2026Review
- SRSF2 mutations drive daunorubicin resistance in acute myeloid leukemia via THBS1 stabilization.Journal of experimental & clinical cancer research : CR · 2026Article
- RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026Review
- Targeting splicing-derived neoantigens for precision cancer immunotherapy.Frontiers in immunology · 2026Review
- Multipurpose RNA maturation factors dysregulate multiple mRNA processing steps simultaneously and provide new therapeutic opportunities.RNA biology · 2025Review
- A Yeast-Based High-Throughput Screening Platform for the Discovery of Novel pre-mRNA Splicing Modulators.bioRxiv : the preprint server for biology · 2025Article
- Splicing Factor Mutations in Chronic Myelomonocytic Leukemia: Biological Consequences and Therapeutic Implications.Current hematologic malignancy reports · 2025Review
- The role of ASXL1, SRSF2, and EZH2 mutations in chromatin dysregulation of myelodysplastic neoplasia and acute myeloid leukemia.Leukemia · 2025Review
- The human branchpoint-interacting stem loop sequence and structure regulates U2 snRNA expression, branchpoint recognition, and transcriptome.bioRxiv : the preprint server for biology · 2025Article
103 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Serine/arginine-rich splicing factor 2 (SRSF2) is an RNA-binding protein that plays important roles in splicing of mRNA precursors. SRSF2 mutations are frequently found in patients with myelodysplastic syndromes and certain leukemias, but how these mutations affect SRSF2 function has only begun to be examined. We used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease to introduce the P95H mutation to SRSF2 in K562 leukemia cells, generating an isogenic model so that splicing alterations can be attributed solely to mutant SRSF2. We found that SRSF2 (P95H) misregulates 548 splicing events (<1% of total). Of these events, 374 involved the inclusion of cassette exons, and the inclusion was either increased (206) or decreased (168). We detected a specific motif (UCCA/UG) enriched in the more-included exons and a distinct motif (UGGA/UG) in the more-excluded exons. RNA gel shift assays showed that a mutant SRSF2 derivative bound more tightly than its wild-type counterpart to RNA sites containing UCCAG but bound less tightly to UGGAG sites. Thus in most cases the pattern of exon inclusion or exclusion correlated with stronger or weaker RNA binding, respectively. We further show that the P95H mutation does not affect other functions of SRSF2, i.e., protein-protein interactions with key splicing factors. Our results thus demonstrate that the P95H mutation positively or negatively alters the binding affinity of SRSF2 for cognate RNA sites in target transcripts, leading to misregulation of exon inclusion. Our findings shed light on the mechanism of the disease-associated SRSF2 mutation in splicing regulation and also reveal a group of misspliced mRNA isoforms for potential therapeutic targeting.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.