ArticleNature chemical biology2007
Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA.
Article in Nature chemical biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 385 papers.
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Who cites it
385 citing papers in PubMed, 651 citations in OpenAlex.
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- Nuclear speckles: a fundamental layer of gene regulation.Trends in cell biology · 2026Review
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- PKR engages viral RNA and intron-retained host transcripts during poxvirus infection.Cell reports · 2026Article
- Alternative Splicing in Cyclin-Dependent Kinase 4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer.Drug development research · 2026Review
- The competition between splicing and 3' processing shapes the human transcriptome.Genes & development · 2026Article
- Inhibition of RNA splicing is a novel therapeutic strategy for disruption of nuclear replicating viruses.bioRxiv : the preprint server for biology · 2026Article
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Spirocyclic β-lactone secondary metabolites modulate spliceosome function.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Integrative CRISPR Screening and RNA Analyses Discover an Essential Role for PUF60 Interactions with 3' Splice Sites in Cancer Progression.Cancer research · 2026Article
- CDK11 inhibition induces cytoplasmic p21Molecular oncology · 2026Article
- Regulation of RNA-binding proteins by small biomolecules.Nature reviews. Molecular cell biology · 2026Review
- Genome minimization of a Burkholderia bacterial host.Metabolic engineering · 2026Article
- Unraveling the FGFR-RNA splicing axis: Mechanisms, oncogenic crosstalks and innovations for therapeutic purpose.Acta pharmaceutica Sinica. B · 2026Review
- RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026Review
- Alternative splicing: from tumorigenesis to neoantigen-mediated cancer immunotherapy.Biomarker research · 2025Review
- RNA splicing is required for timely completion of abscission and is modulated by the abscission checkpoint.bioRxiv : the preprint server for biology · 2025Article
- Genome-wide functional annotation and interpretation of splicing variants: toward RNA-targeted therapies.Journal of human genetics · 2025Review
- A common structural mechanism for RNA recognition by the SF3B complex in mRNA splicing and export.Nucleic acids research · 2025Article
- Epigenetic Regulation and Therapeutic Targeting of Alternative Splicing Dysregulation in Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Review
325 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The removal of intervening sequences from transcripts is catalyzed by the spliceosome, a multicomponent complex that assembles on the newly synthesized pre-mRNA. Pre-mRNA translation in the cytoplasm leads to the generation of aberrant proteins that are potentially harmful. Therefore, tight control to prevent undesired pre-mRNA export from the nucleus and its subsequent translation is an essential requirement for reliable gene expression. Here, we show that the natural product FR901464 (1) and its methylated derivative, spliceostatin A (2), inhibit in vitro splicing and promote pre-mRNA accumulation by binding to SF3b, a subcomplex of the U2 small nuclear ribonucleoprotein in the spliceosome. Importantly, treatment of cells with these compounds resulted in leakage of pre-mRNA to the cytoplasm, where it was translated. Knockdown of SF3b by small interfering RNA induced phenotypes similar to those seen with spliceostatin A treatment. Thus, the inhibition of pre-mRNA splicing during early steps involving SF3b allows unspliced mRNA leakage and translation.
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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.