microRNA-122 Dependent Binding of Ago2 Protein to Hepatitis C Virus RNA Is Associated with Enhanced RNA Stability and Translation Stimulation

作者：Conrad K Dominik; Giering Florian; Erfurth Corinna; Neumann Angelina; Fehr Carmen; Meister Gunter; Niepmann Michael^*

来源：PLos One, 2013, 8(2): e56272.

DOI：10.1371/journal.pone.0056272

Translation of Hepatitis C Virus (HCV) RNA is directed by an internal ribosome entry site (IRES) in the 5%26apos;-untranslated region (5%26apos;-UTR). HCV translation is stimulated by the liver-specific microRNA-122 (miR-122) that binds to two binding sites between the stem-loops I and II near the 5%26apos;-end of the 5%26apos;-UTR. Here, we show that Argonaute (Ago) 2 protein binds to the HCV 5%26apos;-UTR in a miR-122-dependent manner, whereas the HCV 3%26apos;-UTR does not bind Ago2. miR-122 also recruits Ago1 to the HCV 5%26apos;-UTR. Only miRNA duplex precursors of the correct length stimulate HCV translation, indicating that the duplex miR-122 precursors are unwound by a complex that measures their length. Insertions in the 5%26apos;-UTR between the miR-122 binding sites and the IRES only slightly decrease translation stimulation by miR-122. In contrast, partially masking the miR-122 binding sites in a stem-loop structure impairs Ago2 binding and translation stimulation by miR-122. In an RNA decay assay, also miR-122-mediated RNA stability contributes to HCV translation stimulation. These results suggest that Ago2 protein is directly involved in loading miR-122 to the HCV RNA and mediating RNA stability and translation stimulation.

• 出版日期2013-2-6