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

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Gemmill, Dannielle L.
Nelson, Corey R.
Badmalia, Maulik D.
Pereira, Higor S.
Kerr, Liam
Wolfinger, Michael T.
Patel, Trushar R.
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Canadian Science Publishing
Zika 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
Open access article. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
Zika virus , 3' terminal region , G-quadruplex , BG4 antibody , DDX17 , Helicase assay
Gemmill, 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.