The mechanism of ribosomal recruitment during translation initiation on Type 2 IRESs
Year: 2025
Type: preprint
Abstract: The encephalomyocarditis virus (EMCV) IRES and other Type 2 IRESs comprise domains H-L and specifically interact with eIF4G/eIF4A through their essential JK domain. However, the JK domain is not sufficient for IRES function, which also requires the preceding domain I of unknown function. To identify interactions that drive ribosomal recruitment of eIF4G/eIF4A-bound Type 2 IRESs, we determined the cryo-EM structure of 48S initiation complexes formed on the EMCV IRES. It revealed that the apical domain I cloverleaf contacts ribosomal proteins uS13 and uS19 via its Id subdomain and that the essential GNRA tetraloop in subdomain Ic interacts directly with the TψC domain of initiator tRNA. Functional assays supported the exceptional role of these interactions for initiation on this IRES. The strong conservation of primary and secondary structures of the apex of domain I among Type 2 IRESs suggests that the reported interactions are a common essential feature of them all.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Structural Analysis of Macromolecular Assemblies, G3897601807, Alternative mechanisms of different stages in eukaryotic translation, Structural Studies of Macromolecular Assemblies Using Cryo-EM, Mechanisms of eukaryotic translation and ribosome-associated mRNA surveillance and protein quality control, IRES-mediated initiation of picornavirus translation
OpenAlex ID: W4411249802