HCV IRES Captures an Actively Translating 80S Ribosome

Takeshi Yokoyama, Kodai Machida, Wakana Iwasaki, Tomoaki Shigeta, Madoka Nishimoto, Mari Takahashi, Ayako Sakamoto, Mayumi Yonemochi, Yoshie Harada, Hideki Shigematsu, Mikako Shirouzu, Hisashi Tadakuma, Hiroaki Imataka, Takuhiro Ito

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1205-1214.e8
JournalMolecular Cell
Volume74
Issue number6
DOIs
Publication statusPublished - 2019 Jun 20
Externally publishedYes

Keywords

  • IRES
  • cryo-EM
  • hepatitis C virus
  • ribosome
  • translation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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