ArticleProceedings of the National Academy of Sciences of the United States of America2008
A high-throughput screening strategy identifies cardiotonic steroids as alternative splicing modulators.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 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
85 citing papers in PubMed, 138 citations in OpenAlex.
- Review
- PCBP1 regulates alternative splicing of AARS2 in congenital cardiomyopathy.Nature cardiovascular research · 2026Article
- RBPMS and RBPMS2 Cooperate to Safeguard Cardiac Splicing.Circulation research · 2025Article
- Design of a GFP reporter for splicing analysis in mammalian cells.Biotechnology reports (Amsterdam, Netherlands) · 2025Article
- The Druggable Transcriptome Project: From Chemical Probes to Precision Medicines.Biochemistry · 2025Review
- High-throughput sensitive screening of small molecule modulators of microexon alternative splicing using dual Nano and Firefly luciferase reporters.Nature communications · 2024Article
- Small molecule regulators of microRNAs identified by high-throughput screen coupled with high-throughput sequencing.Nature communications · 2023Article
- Towards understandings of serine/arginine-rich splicing factors.Acta pharmaceutica Sinica. B · 2023Review
- Article
- Detection and targeting of splicing deregulation in pediatric acute myeloid leukemia stem cells.Cell reports. Medicine · 2023Article
- Reversal of malignant ADAR1 splice isoform switching with Rebecsinib.Cell stem cell · 2023Article
- HiFENS: high-throughput FISH detection of endogenous pre-mRNA splicing isoforms.Nucleic acids research · 2022Article
- Regulating the regulator: a survey of mechanisms from transcription to translation controlling expression of mammalian cell cycle kinase Aurora A.Open biology · 2022Review
- Hepatitis, testicular degeneration, and ataxia in DIDO3-deficient mice with altered mRNA processing.Cell & bioscience · 2022Article
- Tissue-specific expression of myosin phosphatase subunits and isoforms in smooth muscle of mice and humans.American journal of physiology. Regulatory, integrative and comparative physiology · 2022Article
- Two-Color Fluorescent Reporters for Analysis of Alternative Splicing.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Identification of splice regulators of fibronectin-EIIIA and EIIIB by direct measurement of exon usage in a flow-cytometry based CRISPR screen.Scientific reports · 2021Article
- Non-invasive and high-throughput interrogation of exon-specific isoform expression.Nature cell biology · 2021Article
- New approaches to target RNA binding proteins.Current opinion in chemical biology · 2021Review
- Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities.International journal of molecular sciences · 2021Review
25 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
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Alternative splicing has emerged as a promising therapeutic target in a number of human disorders. However, the discovery of compounds that target the splicing reaction has been hindered by the lack of suitable high-throughput screening assays. Conversely, the effects of known drugs on the splicing reaction are mostly unclear and not routinely assessed. We have developed a two-color fluorescent reporter for cellular assays of exon inclusion that can accommodate nearly any cassette exon and minimizes interfering effects from changes in transcription and translation. We used microtubule-associated protein tau (MAPT) exon 10, whose missplicing causes frontotemporal dementia, to test the reporter in screening libraries of known bioactive compounds. These screens yielded several compounds that alter the splicing of the exon, both in the reporter and in the endogenous MAPT mRNA. One compound, digoxin, has long been used in the treatment of heart failure, but was not known to modulate splicing. The positive compounds target different signal transduction pathways, and microarray analysis shows that each compound affects the splicing of a different set of exons in addition to MAPT exon 10. Our results identify currently prescribed cardiotonic steroids as modulators of alternative splicing and demonstrate the feasibility of screening for drugs that alter exon inclusion.
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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.