ArticleGenes & development2018
The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action.
Article in Genes & development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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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
82 citing papers in PubMed, 109 citations in OpenAlex.
- The SF3b complex in cancer: structural basis, molecular mechanisms, and therapeutic opportunities.Blood advances · 2026Review
- GPATCH11 ortholog Sap34 regulates pre-mRNA splicing by interacting with early spliceosomal complexes in Schizosaccharomyces pombe.Scientific reports · 2026Article
- Article
- Proteogenomic characterization of cervical cancer identifies molecular subtypes predictive of clinical outcomes and subtype-specific targets.The Journal of clinical investigation · 2026Article
- Regulation of RNA-binding proteins by small biomolecules.Nature reviews. Molecular cell biology · 2026Review
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026Review
- RNA-binding proteins as therapeutic targets in cancer.RNA biology · 2025Review
- Multipurpose RNA maturation factors dysregulate multiple mRNA processing steps simultaneously and provide new therapeutic opportunities.RNA biology · 2025Review
- A common structural mechanism for RNA recognition by the SF3B complex in mRNA splicing and export.Nucleic acids research · 2025Article
- Determination of trunk neural crest cell fate and susceptibility to splicing perturbation by the DLC1-SF3B1-PHF5A splicing complex.Nature communications · 2025Article
- Review
- SF3B1K700E mutation in human embryonic stem cells causes aberrant expression of immune-related genes.PloS one · 2025Article
- Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.Research (Washington, D.C.) · 2025Review
- Targeting splicing for hematological malignancies therapy.BMC genomics · 2024Review
- A novel ITGB8 transcript variant sustains ovarian cancer cell survival through genomic instability and altered ploidy on a mutant p53 background.Journal of ovarian research · 2024Article
- Pharmacological Inhibition of the Spliceosome SF3b Complex by Pladienolide-B Elicits Craniofacial Developmental Defects in Mouse and Zebrafish.Birth defects research · 2024Article
- Knotted artifacts in predicted 3D RNA structures.PLoS computational biology · 2024Article
- Structural insights into branch site proofreading by human spliceosome.Nature structural & molecular biology · 2024Article
- Small molecules modulating RNA splicing: a review of targets and future perspectives.RSC medicinal chemistry · 2024Review
22 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
17 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Somatic mutations in spliceosome proteins lead to dysregulated RNA splicing and are observed in a variety of cancers. These genetic aberrations may offer a potential intervention point for targeted therapeutics. SF3B1, part of the U2 small nuclear RNP (snRNP), is targeted by splicing modulators, including E7107, the first to enter clinical trials, and, more recently, H3B-8800. Modulating splicing represents a first-in-class opportunity in drug discovery, and elucidating the structural basis for the mode of action opens up new possibilities for structure-based drug design. Here, we present the cryogenic electron microscopy (cryo-EM) structure of the SF3b subcomplex (SF3B1, SF3B3, PHF5A, and SF3B5) bound to E7107 at 3.95 Å. This structure shows that E7107 binds in the branch point adenosine-binding pocket, forming close contacts with key residues that confer resistance upon mutation: SF3B1
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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.