The 3' terminal region of Zika virus RNA contains a conserved G-quadruplex and is unfolded by human DDX17

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dc.contributor.authorGemmill, Dannielle L.
dc.contributor.authorNelson, Corey R.
dc.contributor.authorBadmalia, Maulik D.
dc.contributor.authorPereira, Higor S.
dc.contributor.authorKerr, Liam
dc.contributor.authorWolfinger, Michael T.
dc.contributor.authorPatel, Trushar R.
dc.date.accessioned2024-06-03T20:28:07Z
dc.date.available2024-06-03T20:28:07Z
dc.date.issued2024
dc.descriptionOpen access article. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
dc.description.abstractZika virus (ZIKV) infection remains a worldwide concern, and currently no effective treatments or vaccines are available. Novel therapeutics are an avenue of interest that could probe viral RNA-human protein communication to stop viral replication. One specific RNA structure, G-quadruplexes (G4s), possess various roles in viruses and all domains of life, including transcription and translation regulation and genome stability, and serves as nucleation points for RNA liquid-liquid phase separation. Previous G4 studies on ZIKV using a quadruplex forming G-rich sequences Mapper located a potential G-quadruplex sequence in the 3 terminal region (TR) and was validated structurally using a 25-mer oligo. It is currently unknown if this structure is conserved and maintained in a large ZIKV RNA transcript and its specific roles in viral replication. Using bioinformatic analysis and biochemical assays, we demonstrate that the ZIKV 3 TR G4 is conserved across all ZIKV isolates and maintains its structure in a 3 TR full-length transcript. We further established the G4 formation using pyridostatin and the BG4 G4-recognizing antibody binding assays. Our study also demonstrates that the human DEAD-box helicases, DDX3X132-607 and DDX17135-555, bind to the 3 TR and that DDX17135-555 unfolds the G4 present in the 3 TR. These findings provide a path forward in potential therapeutic targeting of DDX3X or DDX17’s binding to the 3 TR G4 region for novel treatments against ZIKV
dc.identifier.citationGemmill, D. L., Nelson, C. R., Badmalia, M. D., Pereira, H. S., Kerr, L., Wolfinger, M. T., & Patel, T. R. (2024). The 3' terminal region of Zika virus RNA contains a conserved G-quadruplex and is unfolded by human DDX17. Biochemistry and Cell Biology, 102(1), 96-105. https://doi.org/10.1139/bcb-2023-0036
dc.identifier.urihttps://hdl.handle.net/10133/6764
dc.language.isoen
dc.publisherCanadian Science Publishing
dc.publisher.departmentDepartment of Chemistry and Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.institutionUniversity of Vienna
dc.publisher.institutionUniversity of Calgary
dc.publisher.institutionUniversity of Alberta
dc.subjectZika virus
dc.subject3' terminal region
dc.subjectG-quadruplex
dc.subjectBG4 antibody
dc.subjectDDX17
dc.subjectHelicase assay
dc.subject.lcshZika virus infection
dc.subject.lcshQuadruplex nucleic acids
dc.titleThe 3' terminal region of Zika virus RNA contains a conserved G-quadruplex and is unfolded by human DDX17
dc.typeArticle
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