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Hepatitis C virus nonstructural protein NS3 unfolds viral G-quadruplex RNA structures.
| Content Provider | Europe PMC |
|---|---|
| Author | Belachew, Binyam Gao, Jun Byrd, Alicia K. Raney, Kevin D. |
| Copyright Year | 2022 |
| Abstract | Hepatitis C virus (HCV) is a major cause of liver-related diseases and hepatocellular carcinoma. The helicase domain of one of the nonstructural proteins of HCV, NS3 (nonstructural protein 3), is essential for viral replication; however, its specific biological role is still under investigation. Here, we set out to determine the interaction between a purified recombinant full length NS3 and synthetic guanine-rich substrates that represent the conserved G-quadruplex (G4)-forming sequences in the HCV-positive and HCV-negative strands. We performed fluorescence anisotropy binding, G4 reporter duplex unwinding, and G4RNA trapping assays to determine the binding and G4 unfolding activity of NS3. Our data suggest that NS3 can unfold the conserved G4 structures present within the genome and the negative strand of HCV. Additionally, we found the activity of NS3 on a G4RNA was reduced significantly in the presence of a G4 ligand. The ability of NS3 to unfold HCV G4RNA could imply a novel biological role of the viral helicase in replication. |
| ISSN | 00219258 |
| Volume Number | 298 |
| PubMed Central reference number | PMC9582721 |
| Issue Number | 11 |
| PubMed reference number | 36108740 |
| Journal | The Journal of Biological Chemistry [J. Biol. Chem] |
| e-ISSN | 1083351X |
| DOI | 10.1016/j.jbc.2022.102486 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2022-09-13 |
| Access Restriction | Open |
| Rights License | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). © 2022 The Authors |
| Subject Keyword | Hepatitis C virus (HCV) NS3 helicase G-quadruplex G4 ligand RNA helicase RNA virus enzyme kinetics DEPC, diethyl pyrocarbonate G4, G-quadruplex G4RNA, G-quadruplex RNA HCV, hepatitis C virus NS3, nonstructural protein 3 PDS, Pyridostatin |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology Biochemistry |