Structural dynamics of dengue virus UTRs and their cyclization
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Date
2025
Authors
Robinson, Zachary E.
Pereira, Higor Sette
D'Souza, Michael H.
Patel, Trushar R.
Journal Title
Journal ISSN
Volume Title
Publisher
Cell Press
Abstract
The 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.
Description
Open access article. Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International license (CC BY-NC-ND 4.0) applies
Keywords
Dengue virus , Non-coding RNA , SASX , Computational modelling , RNA-RNA interactions , Flavivirus
Citation
Robinson, 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