The circular RNA circATP8B(2) regulates ROS production and antiviral immunity in Drosophila
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved..
We identified and validated a collection of circular RNAs (circRNAs) in Drosophila melanogaster. We show that depletion of the pro-viral circRNA circATP8B(2), but not its linear siblings, compromises viral infection both in cultured Drosophila cells and in vivo. In addition, circATP8B(2) is enriched in the fly gut, and gut-specific depletion of circATP8B(2) attenuates viral replication in an oral infection model. Furthermore, circATP8B(2) depletion results in increased levels of reactive oxygen species (ROS) and enhanced expression of dual oxidase (Duox), which produces ROS. Genetic and pharmacological manipulations of circATP8B(2)-depleted flies that reduce ROS levels rescue the viral replication defects elicited by circATP8B(2) depletion. Mechanistically, circATP8B(2) associates with Duox, and circATP8B(2)-Duox interaction is crucial for circATP8B(2)-mediated modulation of Duox activity. In addition, Gαq, a G protein subunit required for optimal Duox activity, acts downstream of circATP8B(2). We conclude that circATP8B(2) regulates antiviral defense by modulating Duox expression and Duox-dependent ROS production.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Cell reports - 43(2024), 4 vom: 23. Apr., Seite 113973 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liang, Weihong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.04.2024 Date Revised 26.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2024.113973 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Liang, Weihong |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The circular RNA circATP8B(2) regulates ROS production and antiviral immunity in Drosophila |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 26.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a We identified and validated a collection of circular RNAs (circRNAs) in Drosophila melanogaster. We show that depletion of the pro-viral circRNA circATP8B(2), but not its linear siblings, compromises viral infection both in cultured Drosophila cells and in vivo. In addition, circATP8B(2) is enriched in the fly gut, and gut-specific depletion of circATP8B(2) attenuates viral replication in an oral infection model. Furthermore, circATP8B(2) depletion results in increased levels of reactive oxygen species (ROS) and enhanced expression of dual oxidase (Duox), which produces ROS. Genetic and pharmacological manipulations of circATP8B(2)-depleted flies that reduce ROS levels rescue the viral replication defects elicited by circATP8B(2) depletion. Mechanistically, circATP8B(2) associates with Duox, and circATP8B(2)-Duox interaction is crucial for circATP8B(2)-mediated modulation of Duox activity. In addition, Gαq, a G protein subunit required for optimal Duox activity, acts downstream of circATP8B(2). We conclude that circATP8B(2) regulates antiviral defense by modulating Duox expression and Duox-dependent ROS production | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a CP: Molecular biology | |
| 650 | 4 | |a Drosophila | |
| 650 | 4 | |a Duox | |
| 650 | 4 | |a ROS | |
| 650 | 4 | |a antiviral immunity | |
| 650 | 4 | |a circATP8B(2) | |
| 650 | 4 | |a circular RNA | |
| 650 | 4 | |a non-coding RNA | |
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| 700 | 1 | |a Liu, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Xiao-Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jennifer W |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jian-Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Perera, Ranjan J |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Rui |e verfasserin |4 aut | |
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