Fiche publication
Date publication
avril 2026
Journal
Molecular cell
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MOTORINE Iouri
,
Dr MARCHAND Virginie
Tous les auteurs :
Zhao Y, Rai J, Cohen LN, Shu Y, Xu C, Goswami H, Chen X, Jin H, Marchand V, Motorin Y, Ghalei H, Li H
Lien Pubmed
Résumé
In eukaryotic ribosomes, ∼2% of RNA nucleotides undergo 2'-O-methylation, a conserved cellular mechanism thought to be critical for maintaining and regulating translation. Here, we use ribosome profiling, translation assays, proteomics, and high-resolution structural analyses to show that loss of native 2'-O-methylation in yeast ribosomes disproportionally affects the translation of ribosomal protein transcripts, driven by changes in codon usage and recognition of structured RNA. Translation reprogramming by the hypomethylated ribosomes is supported by reduced thermostability and high-resolution evidence of altered ribosomal structures and conformations. Consistent with the roles of the affected proteins in sustaining cellular fitness, hypomethylated ribosomes under stress exhibit a selective loss of downregulated proteins and misassembly associated with methylation loss. Our data provide structural and mechanistic insights into how 2'-O-methylation supports ribosome integrity and mediates cellular stress responses.
Mots clés
IRES translation, RNA 2′-O-methylation, Ribo-seq, box C/D snoRNPs, fibrillarin, ribosome stability, translation, translation fidelity
Référence
Mol Cell. 2026 04 1;:
