Journal
NUCLEIC ACIDS RESEARCH
Volume 42, Issue 16, Pages 10373-10384Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gku720
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Funding
- Centre National pour la Recherche Scientifique (CNRS, Programme ATIP)
- Agence Nationale de la Recherche contre le Sida [AO12011-11188]
- Universite Paris-Descartes
- Ministere de la Recherche et de l'Enseignement Superieur
- Centre National de la Recherche Scientifique
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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.
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