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

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Chamond, Nathalie | Deforges, Jules | Ulryck, Nathalie | Sargueil, Bruno

Edité par CCSD ; Oxford University Press -

International audience. 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 cur-rent model argues for a mechanism in which the key interaction necessary for the pre-initiation com-plex 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 recruit-ment of the 40S subunit. Importantly, we identified a specific structural element that prevents the cor-rect 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 ear-lier 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 ri-bosome binders, some of which having partly lost the ability to fold into the active structure without the help of proteins.

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