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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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Autores principales: Li, Jia, Fang, Puxian, Zhou, Yanrong, Wang, Dang, Fang, Liurong, Xiao, Shaobo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399600/
https://www.ncbi.nlm.nih.gov/pubmed/36032158
http://dx.doi.org/10.3389/fimmu.2022.956794
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author Li, Jia
Fang, Puxian
Zhou, Yanrong
Wang, Dang
Fang, Liurong
Xiao, Shaobo
author_facet Li, Jia
Fang, Puxian
Zhou, Yanrong
Wang, Dang
Fang, Liurong
Xiao, Shaobo
author_sort Li, Jia
collection PubMed
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.
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spelling pubmed-93996002022-08-25 DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signaling Li, Jia Fang, Puxian Zhou, Yanrong Wang, Dang Fang, Liurong Xiao, Shaobo Front Immunol Immunology 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. Frontiers Media S.A. 2022-08-10 /pmc/articles/PMC9399600/ /pubmed/36032158 http://dx.doi.org/10.3389/fimmu.2022.956794 Text en Copyright © 2022 Li, Fang, Zhou, Wang, Fang and Xiao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Li, Jia
Fang, Puxian
Zhou, Yanrong
Wang, Dang
Fang, Liurong
Xiao, Shaobo
DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signaling
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399600/
https://www.ncbi.nlm.nih.gov/pubmed/36032158
http://dx.doi.org/10.3389/fimmu.2022.956794
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