ArticleNucleic acids research2010
Spliceostatin A inhibits spliceosome assembly subsequent to prespliceosome formation.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
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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.
The trial behind it
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Who cites it
78 citing papers in PubMed.
- PKR engages viral RNA and intron-retained host transcripts during poxvirus infection.Cell reports · 2026Article
- Exon inclusion signatures enable accurate estimation of splicing factor activity.Nature communications · 2026Article
- SF3B1 Phosphorylation Prompts U2AF2 Dissociation for Widespread Control of pre-mRNA Splicing.bioRxiv : the preprint server for biology · 2026Article
- Exon inclusion signatures enable accurate estimation of splicing factor activity.bioRxiv : the preprint server for biology · 2025Article
- High-throughput screen of 100 000 small molecules in C9ORF72 ALS neurons identifies spliceosome modulators that mobilize G4C2 repeat RNA into nuclear export and repeat associated non-canonical translation.Nucleic acids research · 2025Article
- The splicing machinery is dysregulated and represents a therapeutic vulnerability in breast cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Broad variation in response of individual introns to splicing inhibitors in a humanized yeast strain.RNA (New York, N.Y.) · 2024Article
- Broad variation in response of individual introns to splicing inhibitors in a humanized yeast strain.bioRxiv : the preprint server for biology · 2023Article
- Coupling of co-transcriptional splicing and 3' end Pol II pausing during termination in Arabidopsis.Genome biology · 2023Article
- Molecular Threat of Splicing Factor Mutations to Myeloid Malignancies and Potential Therapeutic Modulations.Biomedicines · 2022Review
- 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
- A synthetic small molecule stalls pre-mRNA splicing by promoting an early-stage U2AF2-RNA complex.Cell chemical biology · 2021Article
- Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Herboxidiene Features That Mediate Conformation-Dependent SF3B1 Interactions to Inhibit Splicing.ACS chemical biology · 2021Article
- Design and synthesis of herboxidiene derivatives that potently inhibitOrganic & biomolecular chemistry · 2021Article
- U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors.PloS one · 2021Article
- The SF3b Complex is an Integral Component of the Spliceosome and Targeted by Natural Product-Based Inhibitors.Sub-cellular biochemistry · 2021Review
- Alternative splicing: Human disease and quantitative analysis from high-throughput sequencing.Computational and structural biotechnology journal · 2021Review
- Copper-Catalyzed Stille Cross-Coupling Reaction and Application in the Synthesis of the Spliceostatin Core Structure.The Journal of organic chemistry · 2020Article
- Regulating Divergent Transcriptomes through mRNA Splicing and Its Modulation Using Various Small Compounds.International journal of molecular sciences · 2020Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors.
Funding
Abstract
Pre-mRNA splicing is catalyzed by the large ribonucleoprotein spliceosome. Spliceosome assembly is a highly dynamic process in which the complex transitions through a number of intermediates. Recently, the potent anti-tumor compound Spliceostatin A (SSA) was shown to inhibit splicing and to interact with an essential component of the spliceosome, SF3b. However, it was unclear whether SSA directly impacts the spliceosome and, if so, by what mechanism, which limits interpretation of the drugs influence on splicing. Here, we report that SSA inhibits pre-mRNA splicing by interfering with the spliceosome subsequent to U2 snRNP addition. We demonstrate that SSA inhibition of spliceosome assembly requires ATP, key pre-mRNA splicing sequences and intact U1 and U2 snRNAs. Furthermore all five U snRNAs in addition to the SSA molecule associate with pre-mRNA during SSA inhibition. Kinetic analyses reveal that SSA impedes the A to B complex transition. Remarkably, our data imply that, in addition to its established function in early U2 snRNP recruitment, SF3b plays a role in later maturation of spliceosomes. This work establishes SSA as a powerful tool for dissecting the dynamics of spliceosomes in cells. In addition our data will inform the design of synthetic splicing modulator compounds for targeted anti-tumor treatment.
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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.