GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE227592 Query DataSets for GSE227592
Status Public on Mar 21, 2023
Title ADAR1 biology can hinder effective antiviral RNA interference
Organisms Homo sapiens; Canis lupus familiaris; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Viruses constantly evolve and adapt to the antiviral defenses of their hosts. The biology of viral circumvention of these selective pressures can often be attributed to the acquisition of novel antagonistic gene products or by rapid genome change that prevents host recognition. To study viral evasion of RNA interference (RNAi)-based defenses, we established a robust antiviral system in mammalian cells using recombinant Sendai virus designed to be targeted by endogenous host microRNAs (miRNAs) with perfect complementarity. Using this system, we previously demonstrated the intrinsic ability of positive-strand RNA viruses to escape this selective pressure via homologous recombination, which was not observed in negative-strand RNA viruses. Here we show that given extensive time, escape of miRNA-targeted Sendai virus was enabled by host adenosine deaminase acting on RNA 1 (ADAR1). Independent of the viral transcript targeted, ADAR1 editing resulted in disruption of the miRNA-silencing motif, suggesting an intolerance for extensive RNA:RNA interactions necessary for antiviral RNAi. This was further supported in N. benthamiana, where exogenous expression of ADAR1 interfered with endogenous RNAi. Together, these results suggest that ADAR1 diminishes the effectiveness of RNAi and may explain why it is absent in species that utilize this antiviral defense system.
Overall design RNA-sequencing of mammalian cells lines infected with recombinant Sendai viruses that have sequences with perfectly complemenatrity to host miRNAs added into the 3' UTR of the N gene or P gene to produce an artificial miRNA-based antiviral RNAi. Cell lines, which include A549s, STAT1 KO A549s, STAT1/ADAR1 Double KO A549s, MEFs, and MDCKs were infected and RNA was collected at various timepoints post infection to assess host response and changes to viral genome. Samples where differential gene expression in host cells is assessed are in triplicate.
Contributor(s) Uhl S, tenOever BR
Citation(s) 37017521
Submission date Mar 17, 2023
Last update date Jun 20, 2023
Contact name Skyler Andrew Uhl
Organization name Icahn School of Medicine at Mount Sinai
Department Microbiology
Lab Lim & tenOever labs
Street address 1 Gustave L. levy Pl.
City New York
State/province New York
ZIP/Postal code 10029
Country USA
Platforms (5)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (45)
GSM7103644 WT A549, MOCK, 1dpi,1
GSM7103645 WT A549, MOCK, 1dpi,2
GSM7103646 WT A549, MOCK, 1dpi,3
BioProject PRJNA945880

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
GSE227592_RAW.tar 13.3 Mb (http)(custom) TAR (of CSV, SF)
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