The 3' terminal region of Zika virus RNA contains a conserved G-quadruplex and is unfolded by human DDX17
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Date
2024
Authors
Gemmill, Dannielle L.
Nelson, Corey R.
Badmalia, Maulik D.
Pereira, Higor S.
Kerr, Liam
Wolfinger, Michael T.
Patel, Trushar R.
Journal Title
Journal ISSN
Volume Title
Publisher
Canadian Science Publishing
Abstract
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
Description
Open access article. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
Keywords
Zika virus , 3' terminal region , G-quadruplex , BG4 antibody , DDX17 , Helicase assay
Citation
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. https://doi.org/10.1139/bcb-2023-0036