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Molecular architecture of the ribosome‐bound Hepatitis C Virus internal ribosomal entry site RNA
Author(s) -
Yamamoto Hiroshi,
Collier Marianne,
Loerke Justus,
Ismer Jochen,
Schmidt Andrea,
Hilal Tarek,
Sprink Thiemo,
Yamamoto Kaori,
Mielke Thorsten,
Bürger Jörg,
Shaikh Tanvir R,
Dabrowski Marylena,
Hildebrand Peter W,
Scheerer Patrick,
Spahn Christian MT
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201592469
Subject(s) - biology , ribosome , ribosomal rna , rna , 5.8s ribosomal rna , internal ribosome entry site , virology , microbiology and biotechnology , genetics , gene
Internal ribosomal entry sites ( IRES s) are structured cis ‐acting RNA s that drive an alternative, cap‐independent translation initiation pathway. They are used by many viruses to hijack the translational machinery of the host cell. IRES s 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• HCV IRES complex reveals dynamic conformational modes of the complex. At a global resolution of 3.9 Å 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.