Conrad, K. Dominik and Giering, Florian and Erfurth, Corinna and Neumann, Angelina and Fehr, Carmen and Meister, Gunter and Niepmann, Michael (2013) microRNA-122 Dependent Binding of Ago2 Protein to Hepatitis C Virus RNA Is Associated with Enhanced RNA Stability and Translation Stimulation. PLOS ONE, 8 (2): e56272. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Translation of Hepatitis C Virus (HCV) RNA is directed by an internal ribosome entry site (IRES) in the 5'-untranslated region (5'-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'-end of the 5'-UTR. Here, we show that Argonaute (Ago) 2 protein binds to the HCV 5'-UTR in a miR-122-dependent manner, whereas the HCV 3'-UTR does not bind Ago2. miR-122 also recruits Ago1 to the HCV 5'-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'-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LONG-RANGE RNA; 3'-UNTRANSLATED REGION; RIBOSOME; INITIATION; ELEMENT; IDENTIFICATION; STABILIZATION; ACTIVATION; REPRESSION; MECHANISM; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Apr 2020 10:52 |
| Last Modified: | 24 Apr 2020 10:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17158 |
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