Article
- The EMBO Journal (2007) 26, 795 - 805
- doi:10.1038/sj.emboj.7601549
Published online: 25 January 2007
Subject Categories:
HCV and CSFV IRES domain II mediate eIF2 release during 80S ribosome assembly
Nicolas Locker1, Laura E Easton1 and Peter J Lukavsky1
- MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
Correspondence to:
Peter J Lukavsky, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. Tel.: +44 1223 402417; Fax: +44 1223 213556; E-mail: pjl@mrc-lmb.cam.ac.uk
Received 11 August 2006; Accepted 15 December 2006
Abstract
Internal ribosome entry site (IRES) RNAs from the hepatitis C virus (HCV) and classical swine fever virus (CSFV) coordinate cap-independent assembly of eukaryotic 48S initiation complexes, consisting of the 40S ribosomal subunit, eukaryotic initiation factor (eIF) 3 and the eIF2/GTP/Met-tRNAiMet ternary complex. Here, we report that these IRESes also play a functional role during 80S ribosome assembly downstream of 48S complex formation, in promoting eIF5-induced GTP hydrolysis and eIF2/GDP release from the initiation complex. We show that this function is encoded in their independently folded IRES domain II and that it depends both on its characteristic bent conformation and two conserved RNA motifs, an apical hairpin loop and a loop E. Our data suggest a general mode of subunit joining in HCV and HCV-like IRESes.
Keywords:
- eukaryotic initiation factors,
- HCV,
- IRES RNA,
- RNA structure,
- translation initiation
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