ArticleRNA (New York, N.Y.)2012
The cardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B.
Article in RNA (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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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
43 citing papers in PubMed, 71 citations in OpenAlex.
- Species-specific chromatin architecture and neurogenesis mediated by a human enhancer.Cell stem cell · 2026Article
- Computational Splicing Analysis of Transcriptomic Data Reveals Sulforaphane Modulation of Alternative mRNA Splicing of DNA Repair Genes in Differentiated SH-SY5Y Neurons.International journal of molecular sciences · 2025Article
- Transcriptome-wide alternative mRNA splicing analysis reveals post-transcriptional regulation of neuronal differentiation.The FEBS journal · 2025Article
- Article
- Regulatory interplay between SR proteins governsRNA (New York, N.Y.) · 2024Article
- A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing.Nature cell biology · 2024Article
- Towards understandings of serine/arginine-rich splicing factors.Acta pharmaceutica Sinica. B · 2023Review
- Serine-arginine protein kinases and their targets in viral infection and their inhibition.Cellular and molecular life sciences : CMLS · 2023Review
- Review
- Oncogenic SRSF3 in health and diseases.International journal of biological sciences · 2023Review
- Characterization of alternative mRNA splicing in cultured cell populations representing progressive stages of human fetal kidney development.Scientific reports · 2022Article
- Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latency.Retrovirology · 2022Article
- Localization and functions of native and eGFP-tagged capsid proteins in HIV-1 particles.PLoS pathogens · 2022Article
- ERG transcription factors have a splicing regulatory function involving RBFOX2 that is altered in the EWS-FLI1 oncogenic fusion.Nucleic acids research · 2021Article
- Single-Cell RNA Sequencing Reveals mRNA Splice Isoform Switching during Kidney Development.Journal of the American Society of Nephrology : JASN · 2020Article
- rMAPS2: an update of the RNA map analysis and plotting server for alternative splicing regulation.Nucleic acids research · 2020Article
- Integrative network analysis identifies cell-specific trans regulators of m6A.Nucleic acids research · 2020Article
- An activator of G protein-coupled receptor and MEK1/2-ERK1/2 signaling inhibits HIV-1 replication by altering viral RNA processing.PLoS pathogens · 2020Article
- Pluripotent Stem Cell-Based Drug Screening Reveals Cardiac Glycosides as Modulators of Myotonic Dystrophy Type 1.iScience · 2019Article
- Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism requiring MEK1/2-ERK1/2 signaling.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Modulation of alternative pre-mRNA splicing is a potential approach to therapeutic targeting for a variety of human diseases. We investigated the mechanism by which digitoxin, a member of the cardiotonic steroid class of drugs, regulates alternative splicing. Transcriptome-wide analysis identified a large set of alternative splicing events that change after digitoxin treatment. Within and adjacent to these regulated exons, we identified enrichment of potential binding sites for the splicing factors SRp20 (SRSF3/SFRS3) and Tra2-β (SFRS10/TRA2B). We further find that both of these proteins are depleted from cells by digitoxin treatment. Characterization of SRp20 and Tra2-β splicing targets revealed that many, but not all, digitoxin-induced splicing changes can be attributed to the depletion of one or both of these factors. Re-expression of SRp20 or Tra2-β after digitoxin treatment restores normal splicing of their targets, indicating that the digitoxin effect is directly due to these factors. These results demonstrate that cardiotonic steroids, long prescribed in the clinical treatment of heart failure, have broad effects on the cellular transcriptome through these and likely other RNA binding proteins. The approach described here can be used to identify targets of other potential therapeutics that act as alternative splicing modulators.
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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.