Hepatitis C virus (HCV) replication requires annealing of a liver specific small-RNA, miR-122 to 2 sites on 5′ untranslated region (UTR). Annealing has been reported to (a) stabilize the genome, (b) stimulate translation and (c) promote the formation of translationally active Internal Ribosome Entry Site (IRES) RNA structure. In this report, we map the RNA element to which small RNA annealing promotes HCV to nucleotides 1–44 and identify the relative impact of small RNA annealing on virus translation promotion and genome stabilization. We mapped the optimal region on the HCV genome to which small RNA annealing promotes virus replication to nucleotides 19–37 and found the efficiency of viral RNA accumulation decreased as annealing moved away from this region. Then, by using a panel of small RNAs that promote replication with varying efficiencies we link the efficiency of lifecycle promotion with translation stimulation. By contrast small RNA annealing stabilized the viral genome even if they did not promote virus replication. Thus, we propose that miR-122 annealing promotes HCV replication by annealing to an RNA element that activates the HCV IRES and stimulates translation, and that miR-122 induced HCV genome stabilization is insufficient alone but enhances virus replication.

中文翻译：

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miR-122和其他小RNA的位置特异性退火定义了丙型肝炎病毒5'UTR调控元件，对病毒翻译和基因组稳定性有明显影响。

丙型肝炎病毒（HCV）复制需要将肝脏特异性小RNA miR-122退火至5'非翻译区（UTR）上的2个位点。据报道，退火能够（a）稳定基因组，（b）刺激翻译，（c）促进翻译活性的内部核糖体进入位点（IRES）RNA结构的形成。在本报告中，我们将小RNA退火将HCV促进HCV的RNA元件定位到第1至44位核苷酸，并确定了小RNA退火对病毒翻译促进和基因组稳定的相对影响。我们在HCV基因组上绘制了一个最佳区域，在该区域中，小RNA退火可促进病毒复制到19-37位核苷酸，并发现随着退火远离该区域，病毒RNA积累的效率降低。然后，通过使用一组以不同效率促进复制的小RNA，我们将生命周期促进效率与翻译刺激联系在一起。相比之下，即使小RNA退火不促进病毒复制，也可以稳定病毒基因组。因此，我们提出miR-122退火通过退火至激活HCV IRES并刺激翻译的RNA元件来促进HCV复制，而miR-122诱导的HCV基因组稳定单独不足，但会增强病毒复制。