Informace o publikaci

Molecular architecture of the ribosome-bound Hepatitis C Virus internal ribosomal entry site RNA

Autoři	YAMAMOTO Hiroshi COLLIER Marianne LOERKE Justus ISMER Jochen SCHMIDT Andrea HILAL Tarek SPRINK Thiemo YAMAMOTO Kaori MIELKE Thorsten BURGER Joerg SHAIKH Tanvir DABROWSKI Marylena HILDEBRAND Peter W. SCHEERER Patrick SPAHN Christian M. T.
Rok publikování	2015
Druh	Článek v odborném periodiku
Časopis / Zdroj	EMBO Journal
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	http://emboj.embopress.org/content/34/24/3042
Doi	http://dx.doi.org/10.15252/embj.201592469
Obor	Biochemie
Klíčová slova	80S ribosome; cryo-electron microscopy; internal initiation; IRES RNA; translational control
Popis	Internal ribosomal entry sites (IRESs) are structured cis-acting RNAs that drive an alternative, cap-independent translation initiation pathway. They are used by many viruses to hijack the translational machinery of the host cell. IRESs facilitate translation initiation by recruiting and actively manipulating the eukaryotic ribosome using only a subset of canonical initiation factor and IRES transacting factors. Here we present cryo-EM reconstructions of the ribosome 80S- and 40S-bound Hepatitis C Virus (HCV) IRES. The presence of four subpopulations for the 80S center dot HCV IRES complex reveals dynamic conformational modes of the complex. At a global resolution of 3.9 angstrom for the most stable complex, a derived atomic model reveals a complex fold of the IRES RNA and molecular details of its interaction with the ribosome. The comparison of obtained structures explains how a modular architecture facilitates mRNA loading and tRNA binding to the P-site. This information provides the structural foundation for understanding the mechanism of HCV IRES RNA-driven translation initiation.