HCV IRES captures an actively translating 80S ribosome
HCV IRES captures an actively translating 80S ribosome
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HCV IRES 捕获活跃翻译的 80S 核糖体
DOI：
10.1016/j.molcel.2019.04.022
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发表时间：
2019
期刊：
影响因子：
16
通讯作者：
Ito Takuhiro
中科院分区：
文献类型：
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作者：
Yokoyama Takeshi;Machida Kodai;Iwasaki Wakana;Shigeta Tomoaki;Nishimoto Madoka;Takahashi Mari;Sakamoto Ayako;Yonemochi Mayumi;Harada Yoshie;Shigematsu Hideki;Shirouzu Mikako;Tadakuma Hisashi;Imataka Hiroaki;Ito Takuhiro
丙型肝炎病毒（HCV）基因组RNA的翻译起始由内部核糖体进入位点（IRES）诱导。我们的冷冻电子显微镜（cryo-EM）分析显示，HCV IRES结合到帽依赖性翻译80 S核糖体的40 S平台的溶剂侧。此外，我们还获得了捕获IRES依赖性翻译80 S核糖体的40 S亚基的HCV IRES的冷冻电镜结构。在阐明的结构中，HCV IRES“体”，除了亚结构域IIIb外，由结构域III组成，与40 S亚基结合，而由结构域II组成的“长臂”保持灵活，不妨碍正在进行的翻译。生化实验表明，帽依赖性翻译核糖体成为一个更好的底物HCV IRES比游离核糖体。因此，一旦正在进行的翻译终止，HCV IRES可能有效地诱导其下游mRNA与捕获的翻译核糖体的翻译起始。
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.