Fiche publication
Date publication
juillet 2026
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr KLAHOLZ Bruno
,
Dr MAGLOTT-ROTH Anne
Tous les auteurs :
von Loeffelholz O, Barchet C, Holvec S, Abou Ramadan A, Protuc C, Maglott-Roth A, de Silva SNT, Hazemann I, Klaholz BP
Lien Pubmed
Résumé
The recognition mechanism of Kozak mRNA, typically comprising purines in the -3 and +4 positions flanking the AUG start codon, has remained enigmatic for decades. To address this fundamental function in eukaryotes during translation initiation, we analysed several cryo-EM structures of human 48S preinitiation complexes with mRNA sequences differing in Kozak activity revealing distinct modes of recognition. The pre-codon triplet forms a fan-like intercalation into the 18S ribosomal RNA (rRNA), while a -3 pyrimidine destabilizes ternary complex positioning. Specificity towards the +4 purine is achieved beyond a single residue recognition by mutual conformational adaptations of eIF1A, mRNA and rRNA that involve the insertion of a reading head in which decoding residue A1825 (rRNA) stacks with the A-site codon to stabilize the fully accommodated state. Hence, instead of relying on base pairing as in bacteria, the specific recognition of the Kozak sequence on eukaryotic ribosomes is based on an induced-fit mechanism that triggers a conformational readout of the mRNA.
Référence
Nat Commun. 2026 07 8;:
