ArticleNucleic acids research2013
Pyrvinium pamoate changes alternative splicing of the serotonin receptor 2C by influencing its RNA structure.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Alternative Splicing Regulation in Metabolic Disorders.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Article
- C/D box snoRNAs in viral infections: RNA viruses use old dogs for new tricks.Non-coding RNA research · 2019Review
- Insights into the development of chemical probes for RNA.Nucleic acids research · 2018Article
- The activity of the serotonin receptor 2C is regulated by alternative splicing.Human genetics · 2017Review
- C/D-box snoRNAs form methylating and non-methylating ribonucleoprotein complexes: Old dogs show new tricks.BioEssays : news and reviews in molecular, cellular and developmental biology · 2017Review
- A short history of the 5-HTPsychopharmacology · 2017Review
- Oligonucleotide-induced alternative splicing of serotonin 2C receptor reduces food intake.EMBO molecular medicine · 2016Article
- SNORD116 and SNORD115 change expression of multiple genes and modify each other's activity.Gene · 2015Article
- The Supraspliceosome - A Multi-Task Machine for Regulated Pre-mRNA Processing in the Cell Nucleus.Computational and structural biotechnology journal · 2014Review
- Pyrvinium attenuates Hedgehog signaling downstream of smoothened.Cancer research · 2014Article
- Article
- Interplay between pre-mRNA splicing and microRNA biogenesis within the supraspliceosome.Nucleic acids research · 2014Article
- Spinal muscular atrophy: an update on therapeutic progress.Biochimica et biophysica acta · 2013Review
- An intronic structure enabled by a long-distance interaction serves as a novel target for splicing correction in spinal muscular atrophy.Nucleic acids research · 2013Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
The serotonin receptor 2C plays a central role in mood and appetite control. It undergoes pre-mRNA editing as well as alternative splicing. The RNA editing suggests that the pre-mRNA forms a stable secondary structure in vivo. To identify substances that promote alternative exons inclusion, we set up a high-throughput screen and identified pyrvinium pamoate as a drug-promoting exon inclusion without editing. Circular dichroism spectroscopy indicates that pyrvinium pamoate binds directly to the pre-mRNA and changes its structure. SHAPE (selective 2'-hydroxyl acylation analysed by primer extension) assays show that part of the regulated 5'-splice site forms intramolecular base pairs that are removed by this structural change, which likely allows splice site recognition and exon inclusion. Genome-wide analyses show that pyrvinium pamoate regulates >300 alternative exons that form secondary structures enriched in A-U base pairs. Our data demonstrate that alternative splicing of structured pre-mRNAs can be regulated by small molecules that directly bind to the RNA, which is reminiscent to an RNA riboswitch.
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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.