Department of Medicine, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
RNA Biol. 2013 Jun;10(6):919-23. doi: 10.4161/rna.25137. Epub 2013 May 22.
MicroRNA-122 (miR-122) plays a key role in hepatitis C virus (HCV) replication, but understanding exactly how it functions in the viral lifecycle has been elusive. HCV is a positive-strand virus with a messenger-sense RNA genome, to which miR-122 binds in a non-canonical fashion at two sites near the 5' end. Recent studies show that miR-122 recruits Ago-2 to the genomic RNA, stabilizing it and slowing its decay in infected cells. This led us to investigate decay pathways that mediate degradation of the viral RNA. We found HCV RNA is degraded primarily by the cytoplasmic 5' exonuclease Xrn1 in infected cells. miR-122 lost its stabilizing effect when cells were depleted of Xrn1 using an RNAi strategy, providing strong evidence that miR-122 acts to protect the viral RNA from Xrn1-mediated 5' exonucleolytic decay. However, Xrn1 depletion did not rescue replication of a viral mutant defective in miR-122 binding, indicating that there is much more to miR-122's actions than prevention of Xrn1 decay. Here, we consider the role of miR-122 in the viral lifecycle, and explore the possibility that it might function directly in viral RNA synthesis.
微 RNA-122 (miR-122) 在丙型肝炎病毒 (HCV) 复制中发挥着关键作用，但确切了解其在病毒生命周期中的作用一直难以捉摸。HCV 是一种正链病毒，具有信使 sense RNA 基因组，miR-122 以非规范的方式在 5' 端附近的两个位点与 HCV 结合。最近的研究表明，miR-122 招募 Ago-2 到基因组 RNA 上，稳定它并减缓其在感染细胞中的降解。这促使我们研究介导病毒 RNA 降解的降解途径。我们发现 HCV RNA 主要在感染细胞中被细胞质 5' 外切核酸酶 Xrn1 降解。当使用 RNAi 策略耗尽细胞中的 Xrn1 时，miR-122 失去了其稳定作用，这为 miR-122 作用于保护病毒 RNA 免受 Xrn1 介导的 5' 外切核酸酶降解提供了有力证据。然而，Xrn1 耗尽并不能挽救 miR-122 结合缺陷的病毒突变体的复制，表明 miR-122 的作用远不止于防止 Xrn1 降解。在这里，我们考虑 miR-122 在病毒生命周期中的作用，并探讨其可能直接作用于病毒 RNA 合成的可能性。
