Issue 4, 2024

Small molecules modulating RNA splicing: a review of targets and future perspectives

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.

Graphical abstract: Small molecules modulating RNA splicing: a review of targets and future perspectives

Article information

Article type
Review Article
Submitted
05 dek 2023
Accepted
03 yan 2024
First published
11 yan 2024

RSC Med. Chem., 2024,15, 1109-1126

Small molecules modulating RNA splicing: a review of targets and future perspectives

L. Bouton, A. Ecoutin, F. Malard and S. Campagne, RSC Med. Chem., 2024, 15, 1109 DOI: 10.1039/D3MD00685A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements