40S recruitment in the absence of eIF4G/4A by EMCV IRES refines the model for translation initiation on the archetype of Type II IRESs. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nucleic Acids Research Année : 2014

40S recruitment in the absence of eIF4G/4A by EMCV IRES refines the model for translation initiation on the archetype of Type II IRESs.

Résumé

Initiation of translation on Type II IRESs, such as those of EMCV and FMDV viruses, has been well documented in the recent years. For EMCV, the current model argues for a mechanism in which the key interaction necessary for the pre-initiation complex recruitment is eIF4G binding to the central J-K domains of EMCV-IRES. Here we demonstrate that, in contrast with the current model, the molecular mechanism of EMCV-IRES involves direct recruitment of the 40S subunit. Importantly, we identified a specific structural element that prevents the correct positioning of the initiation codon in the close vicinity of the ribosomal P site. This work clarifies how this interaction could not be anticipated by earlier studies and allows us to propose a new model for initiation complex assembly on EMCV-IRES. The role attributed to eIF4G/4A can thus be refined as stabilizing/promoting the conformational changes that are necessary for IRES function, thus resembling the role conventionally assigned to ITAFs. This raises the interesting possibility that IRESs are primarily ribosome binders, some of which having partly lost the ability to fold into the active structure without the help of proteins.
Fichier principal
Vignette du fichier
10373.full.pdf (2.85 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-01067767 , version 1 (24-09-2014)

Identifiants

Citer

Nathalie Chamond, Jules Deforges, Nathalie Ulryck, Bruno Sargueil. 40S recruitment in the absence of eIF4G/4A by EMCV IRES refines the model for translation initiation on the archetype of Type II IRESs.. Nucleic Acids Research, 2014, 42 (16), pp.10373-84. ⟨10.1093/nar/gku720⟩. ⟨hal-01067767⟩

Collections

CNRS INC-CNRS
51 Consultations
62 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More