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Status |
Public on May 15, 2024 |
Title |
The circular RNA circ_ATP8B regulates ROS production and antiviral immunity [RNA-Seq] |
Organism |
Drosophila melanogaster |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Circular RNAs (circRNAs) are widely expressed in eukaryotes. However, only a subset has been functionally characterized. We have identified and validated a collection of circular RNAs in Drosophila melanogaster. We show that the circular RNA circ_ATP8B is induced by viral infection and that depletion of circ_ATP8B, but not its linear sibling, compromises viral infection both in cultured cells and in vivo. In addition, our analyses reveal that circ_ATP8B is enriched in the fly gut and that gut-specific depletion of circ_ATP8B attenuates viral replication in an oral infection model. Furthermore, we find circ_ATP8B-depletion resulted in increased levels of reactive oxygen species (ROS) and enhanced expression of Duox (Dual oxidase), which produces ROS. Genetic and pharmacological manipulation of circ_ATP8B-depleted flies that reduce ROS levels rescue the viral replication defects elicited by circ_ATP8B depletion. Notably, circ_ATP8B and Duox associate with each other, and that expression of various versions of circ_ATP8B that are competent in binding Duox, but not a mutant circ_ATP8B that is incapable of binding Duox, restores physiological levels of ROS in circ_ATP8B-depleted cells. Lastly, our data show that Gaq, a subunit of G protein required for optimal Duox activity, acts downstream of circ_ATP8B to regulate Duox activity. We conclude that circ_ATP8B regulates anti-viral immunity by modulating Duox-dependent ROS production.
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Overall design |
This study aims to identify RNAs that are differentially expressed upon depletion of the circular RNA circ_ATP8B in vivo. Flies carrying a shRNA transgene against circ_ATP8B or a control shRNA transgene against GFP were crossed to flies carrying the ubiquitously expressed Actin (Act)-Gal4 driver. Total RNAs were extracted from 4-7 day old male and female Act>shGFP and Act>sh-circ_ATP8B flies and subjected to RNA-seq to identify genes that are impacted by circ_ATP8B depletion.
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Contributor(s) |
Liang W, Liu W, Xiong XP, Li JW, Li JL, Perera RJ, Zhou R |
Citation(s) |
38507406 |
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Submission date |
Nov 27, 2023 |
Last update date |
Jul 11, 2024 |
Contact name |
Rui Zhou |
E-mail(s) |
rzhou13@jhmi.edu
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Organization name |
Johns Hopkins University
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Street address |
REB 4130, 501 6th Ave S
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City |
St Petersburg |
State/province |
FL |
ZIP/Postal code |
33701 |
Country |
USA |
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Platforms (1) |
GPL25244 |
Illumina NovaSeq 6000 (Drosophila melanogaster) |
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Samples (12)
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GSM7918531 |
sh-R41, Male infected, 0 hour, replicate1 |
GSM7918532 |
sh-R41, Male infected, 0 hour, replicate2 |
GSM7918533 |
sh-R41, Male infected, 0 hour, replicate3 |
GSM7918534 |
sh-R41, Female infected, 0 hour, replicate1 |
GSM7918535 |
sh-R41, Female infected, 0 hour, replicate2 |
GSM7918536 |
sh-R41, Female infected, 0 hour, replicate3 |
GSM7918537 |
sh-GFP, Male infected, 0 hour, replicate1 |
GSM7918538 |
sh-GFP, Male infected, 0 hour, replicate2 |
GSM7918539 |
sh-GFP, Male infected, 0 hour, replicate3 |
GSM7918540 |
sh-GFP, Female infected, 0 hour, replicate1 |
GSM7918541 |
sh-GFP, Female infected, 0 hour, replicate2 |
GSM7918542 |
sh-GFP, Female infected, 0 hour, replicate3 |
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This SubSeries is part of SuperSeries: |
GSE248667 |
The circular RNA circ_ATP8B regulates ROS production and antiviral immunity |
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Relations |
BioProject |
PRJNA1045542 |
Supplementary file |
Size |
Download |
File type/resource |
GSE248665_circ_ATP8B_RPKM.txt.gz |
979.2 Kb |
(ftp)(http) |
TXT |
GSE248665_circ_ATP8B_counts.txt.gz |
311.6 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
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