ArticleGenes & development2016
SF3B1/Hsh155 HEAT motif mutations affect interaction with the spliceosomal ATPase Prp5, resulting in altered branch site selectivity in pre-mRNA splicing.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review.Journal of cancer research and clinical oncology · 2023Pooled it
- A common structural mechanism for RNA recognition by the SF3B complex in mRNA splicing and export.Nucleic acids research · 2025Article
- Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SF3B1: from core splicing factor to oncogenic driver.RNA (New York, N.Y.) · 2025Review
- Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects ofGenome research · 2024Article
- Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing.bioRxiv : the preprint server for biology · 2024Article
- Aberrant spliceosome activity via elevated intron retention and upregulation and phosphorylation of SF3B1 in chronic lymphocytic leukemia.Molecular therapy. Nucleic acids · 2024Article
- GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in hematologic malignancies.Molecular cell · 2024Article
- Structural insights into branch site proofreading by human spliceosome.Nature structural & molecular biology · 2024Article
- Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape.Molecular cell · 2024Article
- Biochemistry and Protein Interactions of the CYREN Microprotein.Biochemistry · 2023Article
- Article
- Regulation of Pre-mRNA Splicing: Indispensable Role of Post-Translational Modifications of Splicing Factors.Life (Basel, Switzerland) · 2023Review
- Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly.Nature communications · 2023Article
- Pre-mRNA splicing-associated diseases and therapies.RNA biology · 2023Review
- Impacts and mechanisms of alternative mRNA splicing in cancer metabolism, immune response, and therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Structural basis of branch site recognition by the human spliceosome.Science (New York, N.Y.) · 2022Article
- Two oppositely-charged sf3b1 mutations cause defective development, impaired immune response, and aberrant selection of intronic branch sites in Drosophila.PLoS genetics · 2021Article
- Evidence for complex dynamics during U2 snRNP selection of the intron branchpoint.Nucleic acids research · 2021Article
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations in the U2 snRNP component SF3B1 are prominent in myelodysplastic syndromes (MDSs) and other cancers and have been shown recently to alter branch site (BS) or 3' splice site selection in splicing. However, the molecular mechanism of altered splicing is not known. We show here that hsh155 mutant alleles in Saccharomyces cerevisiae, counterparts of SF3B1 mutations frequently found in cancers, specifically change splicing of suboptimal BS pre-mRNA substrates. We found that Hsh155p interacts directly with Prp5p, the first ATPase that acts during spliceosome assembly, and localized the interacting regions to HEAT (Huntingtin, EF3, PP2A, and TOR1) motifs in SF3B1 associated with disease mutations. Furthermore, we show that mutations in these motifs from both human disease and yeast genetic screens alter the physical interaction with Prp5p, alter branch region specification, and phenocopy mutations in Prp5p. These and other data demonstrate that mutations in Hsh155p and Prp5p alter splicing because they change the direct physical interaction between Hsh155p and Prp5p. This altered physical interaction results in altered loading (i.e., "fidelity") of the BS-U2 duplex into the SF3B complex during prespliceosome formation. These results provide a mechanistic framework to explain the consequences of intron recognition and splicing of SF3B1 mutations found in disease.
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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.