ArticleMolecular cell2023
Targeted high-throughput mutagenesis of the human spliceosome reveals its in vivo operating principles.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 33 citations in OpenAlex.
- Mechanism of spliceosome termination.Nature · 2026Article
- REAL-TIME VISUALIZATION OF SPLICEOSOME ASSEMBLY REVEALS BASIC PRINCIPLES OF 3' SPLICE SITE SELECTION.Research square · 2026Article
- Structural basis of the regulation by CDK11 kinase of early spliceosome activation and evidence for its proofreading by DHX15 helicase.Nature communications · 2026Article
- The tumour suppressor RBM5 activates the helicase DHX15 to regulate splicing.Research square · 2026Article
- The tumour suppressor RBM5 activates the helicase DHX15 to regulate splicing.bioRxiv : the preprint server for biology · 2026Article
- RNA-coupled CRISPR screens reveal ZNF207 as a regulator of LMNA aberrant splicing in progeria.Molecular cell · 2026Article
- Mutational scanning reveals substrate-assisted autoregulation of the WNT destruction complex.bioRxiv : the preprint server for biology · 2025Article
- Insulated piggyBac and FRT vectors for engineering transgenic homozygous and heterozygous eHAP cells.Biology open · 2025Article
- Mutations in the spliceosomal gene SNW1 cause neurodevelopment disorders with microcephaly.The Journal of clinical investigation · 2025Article
- A common structural mechanism for RNA recognition by the SF3B complex in mRNA splicing and export.Nucleic acids research · 2025Article
- Generation of transient totipotent blastomere-like stem cells by short-term high-dose Pladienolide B treatment.Science China. Life sciences · 2025Article
- Structural insights into spliceosome fidelity: DHX35-GPATCH1- mediated rejection of aberrant splicing substrates.Cell 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
- Full-length transcriptome atlas of gallbladder cancer reveals trastuzumab resistance conferred by ERBB2 alternative splicing.Signal transduction and targeted therapy · 2025Article
- Building the first base editors.Nature chemical biology · 2025Article
- Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing.bioRxiv : the preprint server for biology · 2024Article
- Branch site recognition by the spliceosome.RNA (New York, N.Y.) · 2024Review
- Engineering Oncogenic Hotspot Mutations on SF3B1 via CRISPR-Directed PRECIS Mutagenesis.Cancer research communications · 2024Article
- GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in hematologic malignancies.Molecular cell · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
The spliceosome is a staggeringly complex machine, comprising, in humans, 5 snRNAs and >150 proteins. We scaled haploid CRISPR-Cas9 base editing to target the entire human spliceosome and investigated the mutants using the U2 snRNP/SF3b inhibitor, pladienolide B. Hypersensitive substitutions define functional sites in the U1/U2-containing A complex but also in components that act as late as the second chemical step after SF3b is dissociated. Viable resistance substitutions map not only to the pladienolide B-binding site but also to the G-patch domain of SUGP1, which lacks orthologs in yeast. We used these mutants and biochemical approaches to identify the spliceosomal disassemblase DHX15/hPrp43 as the ATPase ligand for SUGP1. These and other data support a model in which SUGP1 promotes splicing fidelity by triggering early spliceosome disassembly in response to kinetic blocks. Our approach provides a template for the analysis of essential cellular machines in humans.
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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.