[Nonsense mutations: from premature stop codons to correction strategies].

Authors

Tiphaine Desvages, Luca Houpe, Fabrice Lejeune

Published in

Medecine sciences : M/S. Volume 42. Issue 10. Pages 801-812. Epub Nov 02, 2026.

Abstract

Nonsense mutations introduce a premature stop codon into the coding sequence, which most often leads to rapid degradation of the mRNA through a quality-control mechanisms known as nonsense-mediated mRNA decay (NMD). This process limits the production of truncated proteins that might otherwise retain partial or even complete function of the original protein. In contrast, read-through, a rare natural phenomenon, allows the ribosome to bypass a premature stop codon and restore the synthesis of a full-length protein. Two main strategies have been developed to artificially stimulate this phenomenon: small molecules (including aminoglycosides and their derivatives, as well as non-aminoglycoside compounds) and suppressor tRNAs. Small molecules are relatively easy to use, but their development is often hindered by toxicity issues or insufficient clinical efficacy. Suppressor tRNAs, on the other hand, offer greater specificity, but their therapeutic application faces challenges related to delivery and stability. This review highlights the promising preclinical results obtained with both approaches and discusses their potential for the treatment of genetic diseases caused by nonsense mutations.

PMID:
42969636
Bibliographic data and abstract were imported from PubMed on 02 Nov 2026.

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