The Israeli acute paralysis virus IRES captures host ribosomes by mimicking a ribosomal state with hybrid tRNAs
The Israeli acute paralysis virus IRES captures host ribosomes by mimicking a ribosomal state with hybrid tRNAs
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DOI：
10.15252/embj.2019102226
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发表时间：
2019-10-14
期刊：
影响因子：
11.4
通讯作者：
Fernandez, Israel S.
中科院分区：
文献类型：
--
作者：
Acosta-Reyes, Francisco;Neupane, Ritam;Fernandez, Israel S.
蜂群崩溃障碍是一种在世界范围内导致蜜蜂种群大量死亡的多方面综合征，广泛分布的Dicistroviridae家族中的一组病毒已被确定为引起蜂群崩溃的病原体。这个病毒家族使用非编码的RNA序列，称为内部核糖体进入位点(IRESS)，以精确地利用宿主机制来生产病毒蛋白。利用单粒子冷冻电子显微镜(Cryo-EM)，我们表征了以色列急性麻痹病毒(IAPV)基因间区的IRES是如何捕获并将翻译的核糖体重定向为病毒RNA信息的。我们重建了两个针对核糖体中IAPV-IRES易位前和易位后状态的体外反应，使我们能够使用图像处理分类方法识别六种结构。在此基础上，我们重建了IAPV-IRES在核糖体中从早期的小亚基招募到最终的易位后状态的轨迹。IRES/核糖体复合体早期承诺进行全球预易位模拟，解释了观察到的IRES的高效率。通过使用RNA干扰技术靶向IAPV-IRES来对抗CD的努力正在进行中，这里提出的结构框架可能有助于进一步完善这些方法。
Colony collapse disorder (CCD) is a multi-faceted syndrome decimating bee populations worldwide, and a group of viruses of the widely distributed Dicistroviridae family have been identified as a causing agent of CCD. This family of viruses employs non-coding RNA sequences, called internal ribosomal entry sites (IRESs), to precisely exploit the host machinery for viral protein production. Using single-particle cryo-electron microscopy (cryo-EM), we have characterized how the IRES of Israeli acute paralysis virus (IAPV) intergenic region captures and redirects translating ribosomes toward viral RNA messages. We reconstituted two in vitro reactions targeting a pre-translocation and a post-translocation state of the IAPV-IRES in the ribosome, allowing us to identify six structures using image processing classification methods. From these, we reconstructed the trajectory of IAPV-IRES from the early small subunit recruitment to the final post-translocated state in the ribosome. An early commitment of IRES/ribosome complexes for global pre-translocation mimicry explains the high efficiency observed for this IRES. Efforts directed toward fighting CCD by targeting the IAPV-IRES using RNA-interference technology are underway, and the structural framework presented here may assist in further refining these approaches.