ArticleThe Journal of biological chemistry2010
Further insights into the roles of GTP and the C terminus of the hepatitis C virus polymerase in the initiation of RNA synthesis.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
- Mutations Identified in the Hepatitis C Virus (HCV) Polymerase of Patients with Chronic HCV Treated with Ribavirin Cause Resistance and Affect Viral Replication Fidelity.Antimicrobial agents and chemotherapy · 2020Trial
- Discovery of 5' NAD capped viral RNAs reveals evolutionary divergent 5' metabolite capping across hepaciviruses.Nature communications · 2026Article
- 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
- Structural insights into polymerase-catalyzed FAD capping of hepatitis C virus RNA.Nature communications · 2025Article
- Insights into In Vitro Adaptation of EV71 and Analysis of Reduced Virulence by In Silico Predictions.Vaccines · 2023Article
- Compartmentalization and regulation of GTP in control of cellular phenotypes.Trends in molecular medicine · 2022Review
- Viral Capsid and Polymerase in Reoviridae.Sub-cellular biochemistry · 2022Article
- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- Mechanistic cross-talk between DNA/RNA polymerase enzyme kinetics and nucleotide substrate availability in cells: Implications for polymerase inhibitor discovery.The Journal of biological chemistry · 2020Review
- Ribosome Pausing at Inefficient Codons at the End of the Replicase Coding Region Is Important for Hepatitis C Virus Genome Replication.International journal of molecular sciences · 2020Article
- Novel guanosine derivatives against Zika virus polymerase in silico.Journal of medical virology · 2020Article
- Recombinant RNA-Dependent RNA Polymerase Complex of Ebola Virus.Scientific reports · 2018Article
- Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases.Viruses · 2018Review
- Article
- Hydrogen/Deuterium Exchange Kinetics Demonstrate Long Range Allosteric Effects of Thumb Site 2 Inhibitors of Hepatitis C Viral RNA-dependent RNA Polymerase.The Journal of biological chemistry · 2016Article
- C-Terminal Auto-Regulatory Motif of Hepatitis C Virus NS5B Interacts with Human VAPB-MSP to Form a Dynamic Replication Complex.PloS one · 2016Article
- Review
- The juxtamembrane sequence of the Hepatitis C virus polymerase can affect RNA synthesis and inhibition by allosteric polymerase inhibitors.Virus genes · 2015Article
- Review
- Dual Allosteric Inhibitors Jointly Modulate Protein Structure and Dynamics in the Hepatitis C Virus Polymerase.Biochemistry · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The hepatitis C virus (HCV) NS5b protein is an RNA-dependent RNA polymerase essential for replication of the viral RNA genome. In vitro and presumably in vivo, NS5b initiates RNA synthesis by a de novo mechanism. Different structural elements of NS5b have been reported to participate in RNA synthesis, especially a so-called "β-flap" and a C-terminal segment (designated "linker") that connects the catalytic core of NS5b to a transmembrane anchor. High concentrations of GTP have also been shown to stimulate de novo RNA synthesis by HCV NS5b. Here we describe a combined structural and functional analysis of genotype 1 HCV-NS5b of strains H77 (subtype 1a), for which no structure has been previously reported, and J4 (subtype 1b). Our results highlight the linker as directly involved in lifting the first boundary to processive RNA synthesis, the formation of the first dinucleotide primer. The transition from this first dinucleotide primer state to processive RNA synthesis requires removal of the linker and of the β-flap with which it is shown to strongly interact in crystal structures of HCV NS5b. We find that GTP specifically stimulates this transition irrespective of its incorporation in neosynthesized RNA.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.