ArticleRNA (New York, N.Y.)2018
Inhibition of SF3B1 by molecules targeting the spliceosome results in massive aberrant exon skipping.
Article in RNA (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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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.
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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
34 citing papers in PubMed, 58 citations in OpenAlex.
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- 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
- Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.Research (Washington, D.C.) · 2025Review
- Intronic RNA secondary structural information captured for the humanNAR genomics and bioinformatics · 2024Article
- Zygotic Splicing Activation of the Transcriptome is a Crucial Aspect of Maternal-to-Zygotic Transition and Required for the Conversion from Totipotency to Pluripotency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- The Nitro Group Reshapes the Effects of Pyrido[3,4-Cancers · 2024Article
- A common cellular response to broad splicing perturbations is characterized by metabolic transcript downregulation driven by the Mdm2-p53 axis.Disease models & mechanisms · 2024Article
- Transcriptome Sequencing Allows Comprehensive Genomic Characterization of Pediatric B-Acute Lymphoblastic Leukemia in an Academic Clinical Laboratory.The Journal of molecular diagnostics : JMD · 2024Article
- Branchpoints as potential targets of exon-skipping therapies for genetic disorders.Molecular therapy. Nucleic acids · 2023Article
- Targeted high-throughput mutagenesis of the human spliceosome reveals its in vivo operating principles.Molecular cell · 2023Article
- Single-cell proteo-genomic reveals a comprehensive map of centrosome-associated spliceosome components.iScience · 2023Article
- Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells.Nature cell biology · 2022Article
- Molecular mechanisms by which splice modulator GEX1A inhibits leukaemia development and progression.British journal of cancer · 2022Article
- Mammalian splicing divergence is shaped by drift, buffering inLife science alliance · 2022Article
- Modulation of RNA splicing associated with Wnt signaling pathway using FD-895 and pladienolide B.Aging · 2022Article
- Splicing modulators elicit global translational repression by condensate-prone proteins translated from introns.Cell chemical biology · 2022Article
- SF3B1 homeostasis is critical for survival and therapeutic response in T cell leukemia.Science advances · 2022Article
- Multi-omics approach to identifying isoform variants as therapeutic targets in cancer patients.Frontiers in oncology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The recent identification of compounds that interact with the spliceosome (sudemycins, spliceostatin A, and meayamycin) indicates that these molecules modulate aberrant splicing via SF3B1 inhibition. Through whole transcriptome sequencing, we have demonstrated that treatment of Rh18 cells with sudemycin leads to exon skipping as the predominant aberrant splicing event. This was also observed following reanalysis of published RNA-seq data sets derived from HeLa cells after spliceostatin A exposure. These results are in contrast to previous reports that indicate that intron retention was the major consequence of SF3B1 inhibition. Analysis of the exon junctions up-regulated by these small molecules indicated that these sequences were absent in annotated human genes, suggesting that aberrant splicing events yielded novel RNA transcripts. Interestingly, the length of preferred downstream exons was significantly longer than the skipped exons, although there was no difference between the lengths of introns flanking skipped exons. The reading frame of the aberrantly skipped exons maintained a ratio of 2:1:1, close to that of the cassette exons (3:1:1) present in naturally occurring isoforms, suggesting negative selection by the nonsense-mediated decay (NMD) machinery for out-of-frame transcripts. Accordingly, genes involved in NMD and RNAs encoding proteins involved in the splicing process were enriched in both data sets. Our findings, therefore, further elucidate the mechanisms by which SF3B1 inhibition modulates pre-mRNA splicing.
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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.