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

Yamamoto, H., Collier, M., Loerke, J., Ismer, J., Schmidt, A., Hilal, T., et al. (2015). Molecular architecture of the ribosome-bound Hepatitis C Virus internal ribosomal entry site RNA. EMBO Journal, 34(24), 3042-3058. doi:10.15252/embj.201592469.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-78F7-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-78F8-A
Genre: Journal Article

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 Creators:
Yamamoto, Hiroshi 1, Author
Collier, Marianne1, Author
Loerke, Justus 1, Author
Ismer, Jochen1, Author
Schmidt, Andrea1, Author
Hilal, Tarek1, Author
Sprink, Thiemo1, Author
Yamamoto, Kaori 1, Author
Mielke, Thorsten1, 2, 3, Author              
Bürger, Jörg1, 2, 3, Author              
Shaikh, Tanvir R. 4, Author
Dabrowski, Marylena1, Author
Hildebrand, Peter W.1, Author
Scheerer, Patrick1, Author
Spahn, Christian M. T. 1, Author
Affiliations:
1Institut für Medizinische Physik und Biophysik, Charité – Universitätsmedizin, Berlin, Germany, ou_persistent22              
2Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479668              
3UltraStrukturNetzwerk, Max Planck Institute for Molecular Genetics, Berlin, Germany, ou_persistent22              
4Structural Biology Programme, CEITEC, Masaryk University, Brno, Czech Republic, ou_persistent22              

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Free keywords: 80S Ribosome; Cryo-electron microscopy; Internal initiation; IRES RNA; Translational control
 Abstract: 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•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.

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Language(s): eng - English
 Dates: 2015-11-242015-12-14
 Publication Status: Published in print
 Pages: -
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 Rev. Method: -
 Identifiers: DOI: 10.15252/embj.201592469
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Title: EMBO Journal
  Other : EMBO J.
Source Genre: Journal
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Publ. Info: Nature Publishing Group
Pages: - Volume / Issue: 34 (24) Sequence Number: - Start / End Page: 3042 - 3058 Identifier: ISSN: 0261-4189
CoNE: /journals/resource/954925497061