ArticleScientific reports2019
Altered splicing and cytoplasmic levels of tRNA synthetases in SF3B1-mutant myelodysplastic syndromes as a therapeutic vulnerability.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- DARS expression in JAK2V617F-positive myeloproliferative neoplasms: immunohistochemical analysis and clinical associations.Annals of hematology · 2026Article
- De novo variants in the splicing factor gene SF3B1 are associated with neurodevelopmental disorders.Nature communications · 2026Article
- Distinct and convergent effects ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The cancer-associated SF3B1Cell death & disease · 2025Article
- Nuclear RNA-related processes modulate the assembly of cytoplasmic RNA granules.Nucleic acids research · 2024Article
- Expression of circular RNAs in myelodysplastic neoplasms and their association with mutations in the splicing factor gene SF3B1.Molecular oncology · 2023Article
- Review
- SF3B1 mutations in myelodysplastic syndromes: A potential therapeutic target for modulating the entire disease process.Frontiers in oncology · 2023Review
- Development and validation of an epithelial-mesenchymal transition-related gene signature for predicting prognosis.World journal of clinical cases · 2022Article
- Cancer-Associated SF3B1 Mutations Confer a BRCA-Like Cellular Phenotype and Synthetic Lethality to PARP Inhibitors.Cancer research · 2022Article
- Dysregulated splicing factor SF3B1 unveils a dual therapeutic vulnerability to target pancreatic cancer cells and cancer stem cells with an anti-splicing drug.Journal of experimental & clinical cancer research : CR · 2021Article
- In Silico Analysis of a Highly Mutated Gene in Cancer Provides Insight into Abnormal mRNA Splicing: Splicing Factor 3B Subunit 1Biomolecules · 2020Article
- The K666N mutation in SF3B1 is associated with increased progression of MDS and distinct RNA splicing.Blood advances · 2020Article
- CRISPR editing of sftb-1/SF3B1 in Caenorhabditis elegans allows the identification of synthetic interactions with cancer-related mutations and the chemical inhibition of splicing.PLoS genetics · 2019Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Myelodysplastic syndromes (MDS) are haematopoietic malignancies that are characterised by a heterogeneous clinical course. In recent years, sequencing efforts have uncovered recurrent somatic mutations within RNA splicing factors, including SF3B1, SRSF2, U2AF1 and ZRSR2. The most frequently mutated gene is SF3B1, mutated in 17% of MDS patients. While SF3B1 mutations and their effects on splicing have been well characterised, much remains to be explored about their more far-reaching effects on cellular homeostasis. Given that mRNA splicing and nuclear export are coordinated processes, we hypothesised that SF3B1 mutation might also affect export of certain mRNAs and that this may represent a targetable pathway for the treatment of SF3B1-mutant MDS. We used CRISPR/Cas9-genome editing to create isogenic cellular models. Comprehensive transcriptome and proteome profiling of these cells identified alterations in the splicing and export of components of the translational machinery, primarily tRNA synthetases, in response to the SF3B1 K700E mutation. While steady-state protein synthesis was unaffected, SF3B1 mutant cells were more sensitive to the clinically-relevant purine analogue, 8-azaguanine. In this study, we also demonstrated that 8-azaguanine affects splicing. Our results suggest that the simultaneous targeting of RNA metabolism and splicing by 8-azaguanine represents a therapeutic opportunity for SF3B1-mutant myelodysplastic syndromes.
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