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

Terrell, J. Ross; Le, Thao T.; Paul, Ananya; Brinton, Margo A.; Wilson, W. David; Poon, Gregory M. K.; Germann, Markus W.; Siemer, Jessica L.

doi:10.1038/s41467-024-49761-5

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

Journal Article · Wed Jun 26 00:00:00 UTC 2024 · Nature Communications

DOI: https://doi.org/10.1038/s41467-024-49761-5 · OSTI ID:2469566

Terrell, J. Ross ^[1];

^[1]; Paul, Ananya ^[1];

^[1]; Wilson, W. David ^[1];

^[1];

^[1]

Georgia State University, Atlanta, GA (United States)

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.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: National Institutes of Health, National Institute of General Medical Sciences (NIGMS); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: SC0012704

OSTI ID:: 2469566

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 15; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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

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