title: 40S recruitment in the absence of eIF4G/4A by EMCV IRES refines the model for translation initiation on the archetype of Type II IRESs.
abstract: 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.
authors.affiliation: CNRS UMR8015, Université Paris Descartes, Paris Cedex 06, 75270, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chamond
authors.affiliation: CNRS UMR8015, Université Paris Descartes, Paris Cedex 06, 75270, France.
authors.forename: Jules
authors.initials: J
authors.lastname: Deforges
authors.affiliation: CNRS UMR8015, Université Paris Descartes, Paris Cedex 06, 75270, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ulryck
authors.affiliation: CNRS UMR8015, Université Paris Descartes, Paris Cedex 06, 75270, France bruno.sargueil@parisdescartes.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sargueil
mesh_terms: D020121:5' Untranslated Regions; D004686:Encephalomyocarditis virus / Q000235:genetics*; D039601:Eukaryotic Initiation Factor-4A / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D008957:Models, Genetic; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D010442:Peptide Chain Initiation, Translational; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D039603:Eukaryotic Initiation Factor-4G; D012367:RNA, Viral; D039601:Eukaryotic Initiation Factor-4A