DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signaling
DEAD-box RNA helicase 21 (DDX21), also known as RHII/Gu, is an ATP-dependent RNA helicase. In addition to playing a vital role in regulating cellular RNA splicing, transcription, and translation, accumulated evidence has suggested that DDX21 is also involved in the regulation of innate immunity. How...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.956794/full |
| _version_ | 1811322683040727040 |
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| author | Jia Li Jia Li Puxian Fang Puxian Fang Yanrong Zhou Yanrong Zhou Dang Wang Dang Wang Liurong Fang Liurong Fang Shaobo Xiao Shaobo Xiao |
| author_facet | Jia Li Jia Li Puxian Fang Puxian Fang Yanrong Zhou Yanrong Zhou Dang Wang Dang Wang Liurong Fang Liurong Fang Shaobo Xiao Shaobo Xiao |
| author_sort | Jia Li |
| collection | DOAJ |
| description | DEAD-box RNA helicase 21 (DDX21), also known as RHII/Gu, is an ATP-dependent RNA helicase. In addition to playing a vital role in regulating cellular RNA splicing, transcription, and translation, accumulated evidence has suggested that DDX21 is also involved in the regulation of innate immunity. However, whether DDX21 induces or antagonizes type I interferon (IFN-I) production has not been clear and most studies have been performed through ectopic overexpression or RNA interference-mediated knockdown. In this study, we generated DDX21 knockout cell lines and found that knockout of DDX21 enhanced Sendai virus (SeV)-induced IFN-β production and IFN-stimulated gene (ISG) expression, suggesting that DDX21 is a negative regulator of IFN-β. Mechanistically, DDX21 competes with retinoic acid-inducible gene I (RIG-I) for binding to double-stranded RNA (dsRNA), thereby attenuating RIG-I-mediated IFN-β production. We also identified that the 217–784 amino acid region of DDX21 is essential for binding dsRNA and associated with its ability to antagonize IFN production. Taken together, our results clearly demonstrated that DDX21 negatively regulates IFN-β production and functions to maintain immune homeostasis. |
| first_indexed | 2024-04-13T13:39:26Z |
| format | Article |
| id | doaj.art-961bb08aa2644859927423b19155ba1f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T13:39:26Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-961bb08aa2644859927423b19155ba1f2022-12-22T02:44:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.956794956794DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signalingJia Li0Jia Li1Puxian Fang2Puxian Fang3Yanrong Zhou4Yanrong Zhou5Dang Wang6Dang Wang7Liurong Fang8Liurong Fang9Shaobo Xiao10Shaobo Xiao11State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, ChinaDEAD-box RNA helicase 21 (DDX21), also known as RHII/Gu, is an ATP-dependent RNA helicase. In addition to playing a vital role in regulating cellular RNA splicing, transcription, and translation, accumulated evidence has suggested that DDX21 is also involved in the regulation of innate immunity. However, whether DDX21 induces or antagonizes type I interferon (IFN-I) production has not been clear and most studies have been performed through ectopic overexpression or RNA interference-mediated knockdown. In this study, we generated DDX21 knockout cell lines and found that knockout of DDX21 enhanced Sendai virus (SeV)-induced IFN-β production and IFN-stimulated gene (ISG) expression, suggesting that DDX21 is a negative regulator of IFN-β. Mechanistically, DDX21 competes with retinoic acid-inducible gene I (RIG-I) for binding to double-stranded RNA (dsRNA), thereby attenuating RIG-I-mediated IFN-β production. We also identified that the 217–784 amino acid region of DDX21 is essential for binding dsRNA and associated with its ability to antagonize IFN production. Taken together, our results clearly demonstrated that DDX21 negatively regulates IFN-β production and functions to maintain immune homeostasis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.956794/fullDEAD-box helicase 21 (DDX21)innate immunitytype I interferon (IFN-I)retinoic acid-inducible gene I (RIG-I)double-stranded RNA (dsRNA) |
| spellingShingle | Jia Li Jia Li Puxian Fang Puxian Fang Yanrong Zhou Yanrong Zhou Dang Wang Dang Wang Liurong Fang Liurong Fang Shaobo Xiao Shaobo Xiao DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signaling Frontiers in Immunology DEAD-box helicase 21 (DDX21) innate immunity type I interferon (IFN-I) retinoic acid-inducible gene I (RIG-I) double-stranded RNA (dsRNA) |
| title | DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signaling |
| title_full | DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signaling |
| title_fullStr | DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signaling |
| title_full_unstemmed | DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signaling |
| title_short | DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signaling |
| title_sort | dead box rna helicase 21 negatively regulates cytosolic rna mediated innate immune signaling |
| topic | DEAD-box helicase 21 (DDX21) innate immunity type I interferon (IFN-I) retinoic acid-inducible gene I (RIG-I) double-stranded RNA (dsRNA) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.956794/full |
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