A complex IRES at the 5'-UTR of a viral mRNA assembles a functional 48S complex via an uAUG intermediate

Taking control of the cellular apparatus for protein production is a requirement for virus progression. To ensure this control, diverse strategies of cellular mimicry and/or ribosome hijacking evolved. The initiation stage of translation is specially targeted as it involves multiple steps and the engagement of numerous initiation factors. The use of structured RNA sequences, calledInternalRibosomalEntrySites (IRES) in viral RNAs is a widespread strategy for the exploitation of eukaryotic initiation. Using a combination of electron cryo-microscopy (cryo-EM) and reconstituted translation initiation assays with native components, we characterized how a novel IRES at the 5'-UTR of a viral RNA assembles a functional initiation complex via an uAUG intermediate. The IRES features a novel extended, multi-domain architecture, circling the 40S head. The structures and accompanying functional data, illustrate the importance of 5'-UTR regions in translation regulation and underline the relevance of the untapped diversity of viral IRESs.
Source: eLife - Category: Biomedical Science Tags: Structural Biology and Molecular Biophysics Source Type: research