Human initiation factor eIF3 subunit b interacts with HCV IRES RNA through its N-terminal RNA recognition motif

Pérard, Julien; Rasia, Rodolfo; Medenbach, Jan; Ayala, Isabel; Boisbouvier, Jérôme; Drouet, Emmanuel; Baudin, Florence

doi:10.1016/j.febslet.2008.11.025

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Volume 583, Issue 1 , Pages 70-74, 5 January 2009

Human initiation factor eIF3 subunit b interacts with HCV IRES RNA through its N-terminal RNA recognition motif

Edited by Gianni Cesareni

Julien Pérard
- Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS (UMR 5233), 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France
Rodolfo Rasia
- Institut de Biologie Structurale (IBS) J.P. Ebel, UJF-CEA-CNRS (UMR 5075), 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France
Jan Medenbach
- European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany
Isabel Ayala
- Institut de Biologie Structurale (IBS) J.P. Ebel, UJF-CEA-CNRS (UMR 5075), 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France
Jérôme Boisbouvier
- Institut de Biologie Structurale (IBS) J.P. Ebel, UJF-CEA-CNRS (UMR 5075), 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France
Emmanuel Drouet
- Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS (UMR 5233), 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France
Florence Baudin
- Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS (UMR 5233), 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France
- European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany
- Corresponding author. Fax: +49 6221 387 8518.

Received 22 October 2008; received in revised form 13 November 2008; accepted 18 November 2008. published online 05 December 2008.

Abstract

Many viral mRNAs contain a 5′-UTR RNA element called internal ribosome-entry site (IRES), which bypasses the requirement of some canonical initiation factors allowing cap-independent translation. The IRES of hepatitis-C virus drives translation by directly recruiting 40S ribosomal subunits and binds to eIF3 which plays a critical role in both cap-dependent and cap-independent translation. However, the molecular basis for eIF3 activity in either case remains enigmatic. Here we report that subunit b of the eIF3 complex directly binds to HCV IRES domain III via its N-terminal-RRM. Because eIF3b was previously shown to be involved in eIF3j binding, biological implications are discussed.

Keywords: eIF3b, HCV IRES RNA, NMR spectroscopy, RNA–protein interaction, Translation initiation