@article{d4e3d78a99e84a86969b8a2bda0d7b30,
title = "HCV IRES Captures an Actively Translating 80S Ribosome",
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.",
keywords = "IRES, cryo-EM, hepatitis C virus, ribosome, translation",
author = "Takeshi Yokoyama and Kodai Machida and Wakana Iwasaki and Tomoaki Shigeta and Madoka Nishimoto and Mari Takahashi and Ayako Sakamoto and Mayumi Yonemochi and Yoshie Harada and Hideki Shigematsu and Mikako Shirouzu and Hisashi Tadakuma and Hiroaki Imataka and Takuhiro Ito",
note = "Funding Information: We thank Prof. Y. Tomari at the University of Tokyo for experimental advice and K. Hanada for technical assistance. This research was supported by Grants-in-Aid for Scientific Research on Innovative Areas “Nascent Chain Biology” (JP15H01548 and JP17H05677 to T.I. and JP26116002 to H.I.), “Live-Protein Dynamics,” (JP15H01656 and JP17H05897 to H.S.) and “Non-coding RNA Neo-taxonomy” (JP26113007 to H.T.) and Grants-in-Aid for Scientific Research (B) (JP16H04756 to T.I., JP15H04324 to H.I., and JP16KT0068 to H.T.) from the Japan Society for the Promotion of Science (JSPS), Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS) ( JP18am0101082 ) from the Japan Agency for Medical Research and Development (AMED), the Takeda Science Foundation , the RIKEN Pioneering Project “Dynamic Structural Biology,” and the Cooperative Research Program of the Institute for Protein Research , Osaka University ( CRa-18-01 to H.T. and T.I.). Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = jun,
day = "20",
doi = "10.1016/j.molcel.2019.04.022",
language = "English",
volume = "74",
pages = "1205--1214.e8",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}
