ArticleJournal of molecular biology2012
A template RNA entry channel in the fingers domain of the poliovirus polymerase.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
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- An Extended Primer Grip of Picornavirus Polymerase Facilitates Sexual RNA Replication Mechanisms.Journal of virology · 2020Article
- A nucleobase-binding pocket in a viral RNA-dependent RNA polymerase contributes to elongation complex stability.Nucleic acids research · 2020Article
- Picornavirus RNA Recombination Counteracts Error Catastrophe.Journal of virology · 2019Article
- Picornaviral polymerase structure, function, and fidelity modulation.Virus research · 2017Review
- An in vitro fluorescence based study of initiation of RNA synthesis by influenza B polymerase.Nucleic acids research · 2017Article
- Poliovirus Polymerase Leu420 Facilitates RNA Recombination and Ribavirin Resistance.Journal of virology · 2016Article
- Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication.Journal of virology · 2016Article
- Allosteric inhibitors of Coxsackie virus A24 RNA polymerase.Bioorganic & medicinal chemistry · 2016Article
- Host-virus interaction: the antiviral defense function of small interfering RNAs can be enhanced by host microRNA-7 in vitro.Scientific reports · 2015Article
- The RNA template channel of the RNA-dependent RNA polymerase as a target for development of antiviral therapy of multiple genera within a virus family.PLoS pathogens · 2015Article
- Structure-function relationships underlying the replication fidelity of viral RNA-dependent RNA polymerases.Journal of virology · 2015Article
- Perturbation in the conserved methyltransferase-polymerase interface of flavivirus NS5 differentially affects polymerase initiation and elongation.Journal of virology · 2015Article
- The crystal structure of a cardiovirus RNA-dependent RNA polymerase reveals an unusual conformation of the polymerase active site.Journal of virology · 2014Article
- Surface for catalysis by poliovirus RNA-dependent RNA polymerase.Journal of molecular biology · 2013Article
- Molecular simulations illuminate the role of regulatory components of the RNA polymerase from the hepatitis C virus in influencing protein structure and dynamics.Biochemistry · 2013Article
- Structural features of a picornavirus polymerase involved in the polyadenylation of viral RNA.Journal of virology · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Positive-strand RNA viruses within the Picornaviridae family express an RNA-dependent RNA polymerase, 3D(pol), that is required for viral RNA replication. Structures of 3D(pol) from poliovirus, coxsackievirus, human rhinoviruses, and other picornaviruses reveal a putative template RNA entry channel on the surface of the enzyme fingers domain. Basic amino acids and tyrosine residues along this entry channel are predicted to form ionic and base stacking interactions with the viral RNA template as it enters the polymerase active site. We generated a series of alanine substitution mutations at these residues in the poliovirus polymerase and assayed their effects on template RNA binding, RNA synthesis initiation, rates of RNA elongation, elongation complex (EC) stability, and virus growth. The results show that basic residues K125, R128, and R188 are important for template RNA binding, while tyrosines Y118 and Y148 are required for efficient initiation of RNA synthesis and for EC stability. Alanine substitutions of tyrosines 118 and 148 at the tip of the 3D(pol) pinky finger drastically decreased the rate of initiation as well as EC stability, but without affecting template RNA binding or RNA elongation rates. Viable poliovirus was recovered from HeLa cells transfected with mutant RNAs; however, mutations that dramatically inhibited template RNA binding (K125A-K126A and R188A), RNA synthesis initiation (Y118A, Y148A), or EC stability (Y118A, Y148A) were not stably maintained in progeny virus. These data identify key residues within the template RNA entry channel and begin to define their distinct mechanistic roles within RNA ECs.
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Registered trials
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