Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA
Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA
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DOI：
10.1126/science.1113329
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发表时间：
2005-09-02
期刊：
影响因子：
56.9
通讯作者：
Sarnow, P
中科院分区：
文献类型：
--
作者：
Jopling, CL;Yi, MK;Sarnow, P
MicroRNA是调节信使RNA（mRNA）表达的小RNA分子。MicroRNA 122（miR-122）在人类肝脏中特异性表达且高度丰富。我们发现，在肝细胞中隔离miR-122导致自主复制的丙型肝炎病毒RNA的显著损失。通过对预测的microRNA结合位点的突变分析和含有补偿突变的miR-122分子的异位表达，揭示了miR-122与病毒基因组5'非编码区之间的遗传相互作用。对复制缺陷型RNA的研究表明，miR-122对mRNA翻译或RNA稳定性没有可检测的影响。因此，miR-122可能促进病毒RNA的复制，这表明miR-122可能是抗病毒干预的靶点。
MicroRNAs are small RNA molecules that regulate messenger RNA (mRNA) expression. MicroRNA 122 (miR-122) is specifically expressed and highly abundant in the human liver. We show that the sequestration of miR-122 in liver cells results in marked loss of autonomously replicating hepatitis C viral RNAs. A genetic interaction between miR-122 and the 5' noncoding region of the viral genome was revealed by mutational analyses of the predicted microRNA binding site and ectopic expression of miR-122 molecules containing compensatory mutations. Studies with replication-defective RNAs suggested that miR-122 did not detectably affect mRNA translation or RNA stability. Therefore, miR-122 is likely to facilitate replication of the viral RNA, suggesting that miR-122 may present a target for antiviral intervention.