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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, Sprink T, Yamamoto K, Mielke T, Bürger J, Shaikh TR, Dabrowski M, Hildebrand PW, Scheerer P, Spahn CM
EMBO J 34 3042-58 (2015)
Cited: 58 times
EuropePMC logo PMID: 26604301

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.

Reviews - 5flx mentioned but not cited (2)

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Articles - 5flx mentioned but not cited (3)

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Articles citing this publication (31)

  1. Dynamic competition between SARS-CoV-2 NSP1 and mRNA on the human ribosome inhibits translation initiation. Lapointe CP, Grosely R, Johnson AG, Wang J, Fernández IS, Puglisi JD. Proc Natl Acad Sci U S A 118 (2021)
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  18. The Initiation Factors eIF2, eIF2A, eIF2D, eIF4A, and eIF4G Are Not Involved in Translation Driven by Hepatitis C Virus IRES in Human Cells. González-Almela E, Williams H, Sanz MA, Carrasco L. Front Microbiol 9 207 (2018)
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  20. Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRES. Pisareva VP, Pisarev AV, Fernández IS. Elife 7 (2018)
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  22. Horizontal gene transfer as a mechanism for the promiscuous acquisition of distinct classes of IRES by avian caliciviruses. Arhab Y, Miścicka A, Pestova TV, Hellen CUT. Nucleic Acids Res 50 1052-1068 (2022)
  23. Human ribosomal protein eS1 is engaged in cellular events related to processing and functioning of U11 snRNA. Gopanenko AV, Malygin AA, Tupikin AE, Laktionov PP, Kabilov MR, Karpova GG. Nucleic Acids Res. 45 9121-9137 (2017)
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