NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE169526 Query DataSets for GSE169526
Status Public on Jun 10, 2021
Title Specific Interaction of DDX6 with an RNA Hairpin in the 3?-UTR of the Dengue Genome Mediates G1 Phase Arrest
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The extent to which viral genomic RNAs interact with host factors and contribute to host response and disease pathogenesis is not well known. Here, we report that the human RNA helicase DDX6 specifically binds to the viral most conserved RNA hairpin in the A3 element in the dengue 3ยด-UTR, with nanomolar affinities. DDX6 CLIP confirmed the interaction in HuH-7 cells infected by dengue virus serotype 2. This interaction requires three conserved residues, Lys307, Lys367, and Arg369, as well as the unstructured extension in the C-terminal domain of DDX6. Interestingly, alanine substitution of these three basic residues resulted in RNA-independent ATPase activity, suggesting a mechanism by which RNA-binding and ATPase activities are coupled in DEAD-box helicases. Furthermore, we applied a cross-omics gene enrichment approach to suggest that DDX6 is functionally related to cell cycle regulation and viral pathogenicity. Indeed, infected cells exhibited cell cycle arrest in G1 phase and a decrease in the early S phase. Exogeneous expression of intact DDX6, but not A3-binding-deficient mutants, alleviated these effects by rescue of the DNA pre-initiation complex expression. Disruption of the DDX6-binding site was found in dengue and Zika live-attenuated vaccine strains. Our results suggested that dengue virus has evolved an RNA aptamer against DDX6 to alter host cell states, and defined DDX6 as a new regulator of G1/S transition.
 
Overall design Next generation sequencing of DENV-2 (16681) infected and uninfected HuH-7 cells in the presence/absence of exogeneous DDX6 expression, in duplicate, using BGISEQ-500RS
 
Contributor(s) Choksupmanee O, Trisakulwattana K
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Mar 24, 2021
Last update date Jun 12, 2021
Contact name Opas Choksupmanee
E-mail(s) opascsmn@gmail.com
Organization name Institute of Molecular Biosciences, Mahidol University
Street address 25/25 Phuttamonthon 4 Rd., Salaya, Phuttamonthon
City Nakhon Pathom
ZIP/Postal code 73170
Country Thailand
 
Platforms (1)
GPL23227 BGISEQ-500 (Homo sapiens)
Samples (8)
GSM5208745 pcDNA rep1
GSM5208746 pcDNA rep2
GSM5208747 pcDNAplus rep1
Relations
BioProject PRJNA716981
SRA SRP311961

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE169526_RAW.tar 3.4 Mb (http)(custom) TAR (of CSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap