About: RNA-dependent RNA polymerase speed and fidelity are not the only determinants of the mechanism or efficiency of recombination

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About: RNA-dependent RNA polymerase speed and fidelity are not the only determinants of the mechanism or efficiency of recombination Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	RNA-dependent RNA polymerase speed and fidelity are not the only determinants of the mechanism or efficiency of recombination
Creator	Zhao, Yan Kim, Hyejeong Woodman, Andrew Arnold, Jamie Ellis, Victor
source	BioRxiv; MedRxiv
abstract	Using the RNA-dependent RNA polymerase (RdRp) from poliovirus (PV) as our model system, we have shown that Lys-359 in motif-D functions as a general acid in the mechanism of nucleotidyl transfer. A K359H (KH) RdRp derivative is slow and faithful relative to wild-type enzyme. In the context of the virus, RdRp-coding sequence evolves, selecting for the following substitutions: I331F (IF, motif-C) and P356S (PS, motif-D). We have evaluated IF-KH, PS-KH, and IF-PS-KH viruses and enzymes. The speed and fidelity of each double mutant are equivalent. Each exhibits a unique recombination phenotype, with IF-KH being competent for copy-choice recombination and PS-KH being competent for forced-copy-choice recombination. Although the IF-PS-KH RdRp exhibits biochemical properties within twofold of wild type, the virus is impaired substantially for recombination in cells. We conclude that there are biochemical properties of the RdRp in addition to speed and fidelity that determine the mechanism and efficiency of recombination. The interwoven nature of speed, fidelity, the undefined property suggested here, and recombination makes it impossible to attribute a single property of the RdRp to fitness. However, the derivatives described here may permit elucidation of the importance of recombination on the fitness of the viral population in a background of constant polymerase speed and fidelity. The availability of a “universal” method to create attenuated viruses for use as vaccine strains would permit a rapid response to outbreaks of newly emerging viruses. Targeting RdRp fidelity has emerged as such a universal approach. However, because polymerase fidelity and speed are inextricably linked, the effort to attribute the attenuated phenotype to a single biochemical property of the RdRp may be futile. Here, we show that this circumstance is even more complex. We provide evidence for the existence of a biochemical parameter that combines with fidelity and speed to govern the mechanism and/or efficiency of recombination. We conclude that the field will be served best by continued emphasis on discovery of manipulatable functions of the RdRp instead of debating the importance of individual properties.
has issue date	2019-09-14(xsd:dateTime)
bibo:doi	10.1101/769224
has license	medrxiv
sha1sum (hex)	ec223563f366aa8ed21ec84d1b0d21a911362cfa
schema:url	https://doi.org/10.1101/769224
resource representing a document's title	RNA-dependent RNA polymerase speed and fidelity are not the only determinants of the mechanism or efficiency of recombination
schema:publication	bioRxiv
resource representing a document's body	covid:ec223563f366aa8ed21ec84d1b0d21a911362cfa#body_text
is schema:about of	named entity 'RdRp' named entity 'slow' named entity 'determine' named entity 'recombination' named entity 'transfer' »more»

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