HCV IRES Captures an Actively Translating 80S Ribosome

Mol Cell. 2019 Jun 20;74(6):1205-1214.e8. doi: 10.1016/j.molcel.2019.04.022. Epub 2019 May 9.


Translation initiation of hepatitis C virus (HCV) genomic RNA is induced by an internal ribosome entry site (IRES). Our cryoelectron microscopy (cryo-EM) analysis revealed that the HCV IRES binds to the solvent side of the 40S platform of the cap-dependently translating 80S ribosome. Furthermore, we obtained the cryo-EM structures of the HCV IRES capturing the 40S subunit of the IRES-dependently translating 80S ribosome. In the elucidated structures, the HCV IRES "body," consisting of domain III except for subdomain IIIb, binds to the 40S subunit, while the "long arm," consisting of domain II, remains flexible and does not impede the ongoing translation. Biochemical experiments revealed that the cap-dependently translating ribosome becomes a better substrate for the HCV IRES than the free ribosome. Therefore, the HCV IRES is likely to efficiently induce the translation initiation of its downstream mRNA with the captured translating ribosome as soon as the ongoing translation terminates.

Keywords: IRES; cryo-EM; hepatitis C virus; ribosome; translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cryoelectron Microscopy
  • Eukaryotic Initiation Factors / chemistry*
  • Eukaryotic Initiation Factors / genetics
  • Eukaryotic Initiation Factors / metabolism
  • HEK293 Cells
  • Hepacivirus / genetics*
  • Hepacivirus / metabolism
  • Host-Pathogen Interactions
  • Humans
  • Internal Ribosome Entry Sites
  • Models, Molecular
  • Nucleic Acid Conformation
  • Peptide Chain Initiation, Translational*
  • RNA, Viral / chemistry*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Ribosome Subunits, Large, Eukaryotic / genetics
  • Ribosome Subunits, Large, Eukaryotic / metabolism
  • Ribosome Subunits, Large, Eukaryotic / ultrastructure*
  • Ribosome Subunits, Small, Eukaryotic / genetics
  • Ribosome Subunits, Small, Eukaryotic / metabolism
  • Ribosome Subunits, Small, Eukaryotic / ultrastructure*


  • Eukaryotic Initiation Factors
  • Internal Ribosome Entry Sites
  • RNA, Viral