Structure of an RNA G-quadruplex from the West Nile virus genome

J. Ross Terrell, Thao T. Le, Ananya Paul, Margo A. Brinton, W. David Wilson, Gregory M. K. Poon, Markus W. Germann () and Jessica L. Siemer ()
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J. Ross Terrell: Georgia State University
Thao T. Le: Georgia State University
Ananya Paul: Georgia State University
Margo A. Brinton: Georgia State University
W. David Wilson: Georgia State University
Gregory M. K. Poon: Georgia State University
Markus W. Germann: Georgia State University
Jessica L. Siemer: Georgia State University

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: Abstract Potential G-quadruplex sites have been identified in the genomes of DNA and RNA viruses and proposed as regulatory elements. The genus Orthoflavivirus contains arthropod-transmitted, positive-sense, single-stranded RNA viruses that cause significant human disease globally. Computational studies have identified multiple potential G-quadruplex sites that are conserved across members of this genus. Subsequent biophysical studies established that some G-quadruplexes predicted in Zika and tickborne encephalitis virus genomes can form and known quadruplex binders reduced viral yields from cells infected with these viruses. The susceptibility of RNA to degradation and the variability of loop regions have made structure determination challenging. Despite these difficulties, we report a high-resolution structure of the NS5-B quadruplex from the West Nile virus genome. Analysis reveals two stacked tetrads that are further stabilized by a stacked triad and transient noncanonical base pairing. This structure expands the landscape of solved RNA quadruplex structures and demonstrates the diversity and complexity of biological quadruplexes. We anticipate that the availability of this structure will assist in solving further viral RNA quadruplexes and provides a model for a conserved antiviral target in Orthoflavivirus genomes.

Date: 2024
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DOI: 10.1038/s41467-024-49761-5

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