Léa Bouton, Agathe Ecoutin, Florian Malard and Sébastien Campagne
{"title":"Small molecules modulating RNA splicing: a review of targets and future perspectives","authors":"Léa Bouton, Agathe Ecoutin, Florian Malard and Sébastien Campagne","doi":"10.1039/D3MD00685A","DOIUrl":null,"url":null,"abstract":"<p >In eukaryotic cells, RNA splicing is crucial for gene expression. Dysregulation of this process can result in incorrect mRNA processing, leading to aberrant gene expression patterns. Such abnormalities are implicated in many inherited diseases and cancers. Historically, antisense oligonucleotides, which bind to specific RNA targets, have been used to correct these splicing abnormalities. Despite their high specificity of action, these oligonucleotides have drawbacks, such as lack of oral bioavailability and the need for chemical modifications to enhance cellular uptake and stability. As a result, recent efforts focused on the development of small organic molecules that can correct abnormal RNA splicing event under disease conditions. This review discusses known and potential targets of these molecules, including RNA structures, <em>trans</em>-acting splicing factors, and the spliceosome – the macromolecular complex responsible for RNA splicing. We also rely on recent advances to discuss therapeutic applications of RNA-targeting small molecules in splicing correction. Overall, this review presents an update on strategies for RNA splicing modulation, emphasizing the therapeutic promise of small molecules.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":null,"pages":null},"PeriodicalIF":3.5970,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"MedChemComm","FirstCategoryId":"1085","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/md/d3md00685a","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 0
Abstract
In eukaryotic cells, RNA splicing is crucial for gene expression. Dysregulation of this process can result in incorrect mRNA processing, leading to aberrant gene expression patterns. Such abnormalities are implicated in many inherited diseases and cancers. Historically, antisense oligonucleotides, which bind to specific RNA targets, have been used to correct these splicing abnormalities. Despite their high specificity of action, these oligonucleotides have drawbacks, such as lack of oral bioavailability and the need for chemical modifications to enhance cellular uptake and stability. As a result, recent efforts focused on the development of small organic molecules that can correct abnormal RNA splicing event under disease conditions. This review discusses known and potential targets of these molecules, including RNA structures, trans-acting splicing factors, and the spliceosome – the macromolecular complex responsible for RNA splicing. We also rely on recent advances to discuss therapeutic applications of RNA-targeting small molecules in splicing correction. Overall, this review presents an update on strategies for RNA splicing modulation, emphasizing the therapeutic promise of small molecules.
期刊介绍:
Research and review articles in medicinal chemistry and related drug discovery science; the official journal of the European Federation for Medicinal Chemistry.
In 2020, MedChemComm will change its name to RSC Medicinal Chemistry. Issue 12, 2019 will be the last issue as MedChemComm.