A complex IRES at the 5'-UTR of a viral mRNA assembles a functional 48S complex via an uAUG intermediate
- Columbia University, United States
- SUNY Downstate Medical Center, United States
- CNIO, Spain
Abstract
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, called Internal Ribosomal Entry Sites (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.
Data availability
Atomic coordinates have been deposited in the PDB with accession numbers and 6W2S and 6W2T. CryoEM maps have been deposited at the EMDB with accession numbers EMDB 21529/21530
Article and author information
Author details
Carlos F Rodriguez
Israel S Fernández
Funding
Columbia University (Start package)
- Israel S Fernández
National Institute of General Medical Sciences (GM097014)
- Andrey V Pisarev
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Neupane et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A complex IRES at the 5'-UTR of a viral mRNA assembles a functional 48S complex via an uAUG intermediate
eLife 9:e54575.
https://doi.org/10.7554/eLife.54575
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