4.6 Article

Deciphering the molecular mechanism of stop codon readthrough

Journal

BIOLOGICAL REVIEWS
Volume 96, Issue 1, Pages 310-329

Publisher

WILEY
DOI: 10.1111/brv.12657

Keywords

stop codon readthrough; mechanism; translation termination; premature termination codon; readthrough activators; molecules; screening

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Funding

  1. Region Hauts-de-France
  2. l'Universite de Lille
  3. Vaincre la mucoviscidose
  4. La Ligue Contre le Cancer
  5. GIP Canceropole Nord Ouest

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Recognition of the stop codon is crucial for terminating translation and synthesizing the correct size protein. Stop codon readthrough can occur under specific conditions, leading to different protein isoforms, and has potential therapeutic implications for genetic diseases caused by nonsense mutations.
Recognition of the stop codon by the translation machinery is essential to terminating translation at the right position and to synthesizing a protein of the correct size. Under certain conditions, the stop codon can be recognized as a coding codon promoting translation, which then terminates at a later stop codon. This event, called stop codon readthrough, occurs either by error, due to a dedicated regulatory environment leading to generation of different protein isoforms, or through the action of a readthrough compound. This review focuses on the mechanisms of stop codon readthrough, the nucleotide and protein environments that facilitate or inhibit it, and the therapeutic interest of stop codon readthrough in the treatment of genetic diseases caused by nonsense mutations.

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