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Nat Struct Mol Biol. 2013 Feb;20(2):150-8. doi: 10.1038/nsmb.2465. Epub 2012 Dec 23.

HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

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1
Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado, USA.

Abstract

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders.

PMID:
23262488
PMCID:
PMC3864654
DOI:
10.1038/nsmb.2465
[Indexed for MEDLINE]
Free PMC Article
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