ArticleThe Journal of biological chemistry2008
Hepatitis C virus NS5B polymerase exhibits distinct nucleotide requirements for initiation and elongation.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Hepatitis C Virus 5'UTR Sequences That Bind eIF3 and Ribosomal 40S Subunits Confer Stimulation of Minus-Strand RNA Synthesis.International journal of molecular sciences · 2026Article
- Evidence for Internal Initiation of RNA Synthesis by the Hepatitis C Virus RNA-Dependent RNA Polymerase NS5BJournal of virology · 2019Article
- Initiation, extension, and termination of RNA synthesis by a paramyxovirus polymerase.PLoS pathogens · 2018Article
- Biophysical Mode-of-Action and Selectivity Analysis of Allosteric Inhibitors of Hepatitis C Virus (HCV) Polymerase.Viruses · 2017Article
- Article
- Cross-genotypic examination of hepatitis C virus polymerase inhibitors reveals a novel mechanism of action for thumb binders.Antimicrobial agents and chemotherapy · 2014Article
- Hepatitis C virus RNA replication and assembly: living on the fat of the land.Cell host & microbe · 2014Review
- Initiation of RNA synthesis by the hepatitis C virus RNA-dependent RNA polymerase is affected by the structure of the RNA template.Biochemistry · 2014Article
- Dynamics of hepatitis C virus (HCV) RNA-dependent RNA polymerase NS5B in complex with RNA.The Journal of biological chemistry · 2014Article
- Discovery of SCH 900188: A Potent Hepatitis C Virus NS5B Polymerase Inhibitor Prodrug As a Development Candidate.ACS medicinal chemistry letters · 2014Article
- Article
- Hepatitis C virus RNA replication.Current topics in microbiology and immunology · 2013Review
- Discovery of new scaffolds for rational design of HCV NS5B polymerase inhibitors.European journal of medicinal chemistry · 2012Article
- Two crucial early steps in RNA synthesis by the hepatitis C virus polymerase involve a dual role of residue 405.Journal of virology · 2012Article
- De novo polymerase activity and oligomerization of hepatitis C virus RNA-dependent RNA-polymerases from genotypes 1 to 5.PloS one · 2011Article
- Pyridine Carboxamides: Potent Palm Site Inhibitors of HCV NS5B Polymerase.ACS medicinal chemistry letters · 2010Article
- Further insights into the roles of GTP and the C terminus of the hepatitis C virus polymerase in the initiation of RNA synthesis.The Journal of biological chemistry · 2010Article
- Article
- Regulation of de novo-initiated RNA synthesis in hepatitis C virus RNA-dependent RNA polymerase by intermolecular interactions.Journal of virology · 2010Article
- Structural and functional analysis of hepatitis C virus strain JFH1 polymerase.Journal of virology · 2009Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatitis C virus (HCV) NS5B protein is an RNA-dependent RNA polymerase (RdRp) essential for replication of the viral RNA genome. Purified NS5B has been reported to exhibit multiple activities in vitro. Using a synthetic heteropolymeric RNA template with dideoxycytidine at its 3'-end, we examined de novo initiation and primer extension in a system devoid of self-priming and terminal nucleotide transferase activities. Products predominantly of template size and its multiples were detected. High concentrations of nucleoside triphosphates (K(app)(m) approximately 100-400 mum) corresponding to the first three incorporated nucleotides were found to be required for efficient de novo RNA synthesis. In the presence of initiating di- or trinucleotides, however, the amount of NTP needed to achieve maximal activity dropped 10(3)- to 10(4)-fold, revealing a much reduced nucleotide requirement for elongation (K(app)(m) approximately 0.03-0.09 microm). Accordingly, single round extension from an exogenous primer following preincubation of the enzyme with template and primer could also be supported by <0.1 microm levels of NTP. De novo synthesis at high NTP concentrations was shown to be preferred over primer extension. On a dideoxycytidine-blocked synthetic RNA template derived from the 3'-end of the HCV(-)UTR, the addition of the corresponding initiating trinucleotide also dramatically reduced the NTP levels needed to achieve efficient RNA synthesis. Thus, distinct nucleotide requirements exist for initiation and elongation steps catalyzed by the HCV NS5B polymerase.
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