Structural dynamics of dengue virus UTRs and their cyclization

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dc.contributor.authorRobinson, Zachary E.
dc.contributor.authorPereira, Higor Sette
dc.contributor.authorD'Souza, Michael H.
dc.contributor.authorPatel, Trushar R.
dc.date.accessioned2025-10-16T20:11:49Z
dc.date.available2025-10-16T20:11:49Z
dc.date.issued2025
dc.descriptionOpen access article. Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International license (CC BY-NC-ND 4.0) applies
dc.description.abstractThe dengue virus (DENV) poses a significant threat to human health, accounting for approximately 400 million infections each year. Its genome features a circular structure that facilitates replication through long-range RNA-RNA interac- tions, utilizing cyclization sequences located in the untranslated regions (UTRs). To gain new insights into the organization of the DENV genome, we purified the 5′ and 3′ UTRs of DENV in vitro and examined their structural and binding properties using various biophysical techniques combined with computational methods. Through our biophysical characterization, we deter- mined the 5′ and 3′ UTR regions to bind with an affinity of 40 nM in a 1:1 stoichiometry. By using small-angle x-ray scattering, we provide the first structural characterization of the 3′ and 5′ UTR regions, revealing several plausible conformations that the viral UTRs may adopt during replication. This comprehensive investigation revealed key features that provide mechanistic in- sights into the different structural states during DENV replication, as tracked through the accessibility of various RNA conforma- tions. Overall, our research enhances the understanding of DENV cyclization, emphasizing the structural adaptability, dynamic folding, and flexibility of these RNA molecules in solution. By uncovering details at the atomic level, we aim to contribute to the development of targeted drugs that can disrupt crucial stages of viral replication.
dc.identifier.citationRobinson, Z. E., Pereira, H. S., D'Souza, M. H. & Patel, Trushar R. (2025). Structural dynamics of dengue virus UTRs and their cyclization. Biophysical Journal. https://doi.org/10.1016/j.bpj.2025.09.004
dc.identifier.urihttps://hdl.handle.net/10133/7172
dc.language.isoen
dc.publisherCell Press
dc.publisher.departmentDepartment of Chemistry and Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.institutionUniversity of Alberta
dc.publisher.institutionUniversity of Calgary
dc.publisher.urlhttps://doi.org/10.1016/j.bpj.2025.09.004
dc.subjectDengue virus
dc.subjectNon-coding RNA
dc.subjectSASX
dc.subjectComputational modelling
dc.subjectRNA-RNA interactions
dc.subjectFlavivirus
dc.titleStructural dynamics of dengue virus UTRs and their cyclization
dc.typeArticle
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