ArticleGenes & development2011
Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A.
Article in Genes & development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 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
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
175 citing papers in PubMed, 270 citations in OpenAlex.
- Review
- The competition between splicing and 3' processing shapes the human transcriptome.Genes & development · 2026Article
- Modulation of splicing factors SF3B1 and SRSF1 by polypurine reverse Hoogsteen hairpins affects the splicing pattern of estrogen receptor α in breast cancer cells.Cancer cell international · 2026Article
- Phosphorylation of SF3B1 by CDK11 orchestrates spliceosome activation via SNIP1-dependent RES complex recruitment.Nature communications · 2026Article
- De novo variants in the splicing factor gene SF3B1 are associated with neurodevelopmental disorders.Nature communications · 2026Article
- Unlocking the undruggable spliceosome: generative AI and structural dynamics in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- RNA-binding proteins as therapeutic targets in cancer.RNA biology · 2025Review
- Article
- RNA splicing is required for timely completion of abscission and is modulated by the abscission checkpoint.bioRxiv : the preprint server for biology · 2025Article
- Article
- The pre-mRNA splicing modulator pladienolide B inhibitsmSphere · 2025Article
- RBM17 promotes hepatocellular carcinoma progression by regulating lipid metabolism and immune microenvironment: implications for therapeutic targeting.Cell death discovery · 2025Article
- Review
- 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
- Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting splicing for hematological malignancies therapy.BMC genomics · 2024Review
- The Impact of Spliceosome Inhibition in SF3B1-Mutated Uveal Melanoma.Investigative ophthalmology & visual science · 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
115 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
Spliceostatin A (SSA) is a stabilized derivative of a Pseudomonas bacterial fermentation product that displays potent anti-proliferative and anti-tumor activities in cancer cells and animal models. The drug inhibits pre-mRNA splicing in vitro and in vivo and binds SF3b, a protein subcomplex of U2 small nuclear ribonucleoprotein (snRNP), which is essential for recognition of the pre-mRNA branch point. We report that SSA prevents interaction of an SF3b 155-kDa subunit with the pre-mRNA, concomitant with nonproductive recruitment of U2 snRNP to sequences 5' of the branch point. Differences in base-pairing potential with U2 snRNA in this region lead to different sensitivity of 3' splice sites to SSA, and to SSA-induced changes in alternative splicing. Indeed, rather than general splicing inhibition, splicing-sensitive microarray analyses reveal specific alternative splicing changes induced by the drug that significantly overlap with those induced by knockdown of SF3b 155. These changes lead to down-regulation of genes important for cell division, including cyclin A2 and Aurora A kinase, thus providing an explanation for the anti-proliferative effects of SSA. Our results reveal a mechanism that prevents nonproductive base-pairing interactions in the spliceosome, and highlight the regulatory and cancer therapeutic potential of perturbing the fidelity of splice site recognition.
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What OpenQuestion holds
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.