ArticleNucleic acids research2018
A unique intra-molecular fidelity-modulating mechanism identified in a viral RNA-dependent RNA polymerase.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Article
- Engineered VPg saRNA achieves cap-independent, low-immunogenic and precise encoding of therapeutic proteins in vivo.Nature communications · 2026Article
- Taxonomic expansion and reorganization of Flaviviridae.Nature microbiology · 2025Article
- Mutation in enterovirus 71 nonstructural protein 3A increases genome replication fidelity and exhibits attenuated virulence in mice.Journal of virology · 2025Article
- Structural insights into polymerase-catalyzed FAD capping of hepatitis C virus RNA.Nature communications · 2025Article
- An evolutionarily unique viral RdRP suggests a common dual-function feature of the priming element.Science advances · 2025Article
- Integrated analysis of protein sequence and structure redefines viral diversity and the taxonomy of thebioRxiv : the preprint server for biology · 2025Article
- Assessment of the Safety Profile of Chimeric Marker Vaccine against Classical Swine Fever: Reversion to Virulence Study.Viruses · 2024Article
- A jingmenvirus RNA-dependent RNA polymerase structurally resembles the flavivirus counterpart but with different features at the initiation phase.Nucleic acids research · 2024Article
- Galidesivir Triphosphate Promotes Stalling of Dengue-2 Virus Polymerase Immediately Prior to Incorporation.ACS infectious diseases · 2023Article
- Unusual substructure conformations observed in crystal structures of a dicistrovirus RNA-dependent RNA polymerase suggest contribution of the N-terminal extension in proper folding.Virologica Sinica · 2023Article
- Structural basis of transition from initiation to elongation in de novo viral RNA-dependent RNA polymerases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Identification of new inhibitors of NS5 from dengue virus using saturation transfer difference (STD-NMR) and molecular docking studies.RSC advances · 2022Article
- Revisiting Viral RNA-Dependent RNA Polymerases: Insights from Recent Structural Studies.Viruses · 2022Review
- The Second Human Pegivirus, a Non-Pathogenic RNA Virus with Low Prevalence and Minimal Genetic Diversity.Viruses · 2022Review
- An induced-fit de novo initiation mechanism suggested by a pestivirus RNA-dependent RNA polymerase.Nucleic acids research · 2021Article
- Characteristics of Classical Swine Fever Virus Variants Derived from Live Attenuated GPEViruses · 2021Article
- Article
- Crystal structure of a tick-borne flavivirus RNA-dependent RNA polymerase suggests a host adaptation hotspot in RNA viruses.Nucleic acids research · 2021Article
- Difference of Intrahost Dynamics of the Second Human Pegivirus and Hepatitis C Virus in HPgV-2/HCV-Coinfected Patients.Frontiers in cellular and infection microbiology · 2021Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Typically not assisted by proofreading, the RNA-dependent RNA polymerases (RdRPs) encoded by the RNA viruses may need to independently control its fidelity to fulfill virus viability and fitness. However, the precise mechanism by which the RdRP maintains its optimal fidelity level remains largely elusive. By solving 2.1-2.5 Å resolution crystal structures of the classical swine fever virus (CSFV) NS5B, an RdRP with a unique naturally fused N-terminal domain (NTD), we identified high-resolution intra-molecular interactions between the NTD and the RdRP palm domain. In order to dissect possible regulatory functions of NTD, we designed mutations at residues Y471 and E472 to perturb key interactions at the NTD-RdRP interface. When crystallized, some of these NS5B interface mutants maintained the interface, while the others adopted an 'open' conformation that no longer retained the intra-molecular interactions. Data from multiple in vitro RdRP assays indicated that the perturbation of the NTD-RdRP interactions clearly reduced the fidelity level of the RNA synthesis, while the processivity of the NS5B elongation complex was not affected. Collectively, our work demonstrates an explicit and unique mode of polymerase fidelity modulation and provides a vivid example of co-evolution in multi-domain enzymes.
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