The protein arginine methyltransferase PRMT1 promotes TBK1 activation through asymmetric arginine methylation

Summary: TBK1 is an essential kinase for the innate immune response against viral infection. However, the key molecular mechanisms regulating the TBK1 activation remain elusive. Here, we identify PRMT1, a type I protein arginine methyltransferase, as an essential regulator of TBK1 activation. PRMT1...

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Main Authors:	Zhenzhen Yan, Haifeng Wu, Hansen Liu, Guimin Zhao, Honghai Zhang, Wanxin Zhuang, Feng Liu, Yi Zheng, Bingyu Liu, Lei Zhang, Chengjiang Gao
Format:	Article
Language:	English
Published:	Elsevier 2021-09-01
Series:	Cell Reports
Subjects:	protein arginine methylation innate antiviral immunity PRMT1 TBK1
Online Access:	http://www.sciencedirect.com/science/article/pii/S2211124721011803

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spelling	doaj-c93b5156152f47cd920b515f62ade9622021-09-23T04:38:37ZengElsevierCell Reports2211-12472021-09-013612109731The protein arginine methyltransferase PRMT1 promotes TBK1 activation through asymmetric arginine methylationZhenzhen Yan0Haifeng Wu1Hansen Liu2Guimin Zhao3Honghai Zhang4Wanxin Zhuang5Feng Liu6Yi Zheng7Bingyu Liu8Lei Zhang9Chengjiang Gao10Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China; Corresponding authorSummary: TBK1 is an essential kinase for the innate immune response against viral infection. However, the key molecular mechanisms regulating the TBK1 activation remain elusive. Here, we identify PRMT1, a type I protein arginine methyltransferase, as an essential regulator of TBK1 activation. PRMT1 directly interacts with TBK1 and catalyzes asymmetric methylation of R54, R134, and R228 on TBK1. This modification enhances TBK1 oligomerization after viral infection, which subsequently promotes TBK1 phosphorylation and downstream type I interferon production. More important, myeloid-specific Prmt1 knockout mice are more susceptible to infection with DNA and RNA viruses than Prmt1fl/fl mice. Our findings reveal insights into the molecular regulation of TBK1 activation and demonstrate the essential function of protein arginine methylation in innate antiviral immunity.http://www.sciencedirect.com/science/article/pii/S2211124721011803protein arginine methylationinnate antiviral immunityPRMT1TBK1
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Zhenzhen Yan Haifeng Wu Hansen Liu Guimin Zhao Honghai Zhang Wanxin Zhuang Feng Liu Yi Zheng Bingyu Liu Lei Zhang Chengjiang Gao
spellingShingle	Zhenzhen Yan Haifeng Wu Hansen Liu Guimin Zhao Honghai Zhang Wanxin Zhuang Feng Liu Yi Zheng Bingyu Liu Lei Zhang Chengjiang Gao The protein arginine methyltransferase PRMT1 promotes TBK1 activation through asymmetric arginine methylation Cell Reports protein arginine methylation innate antiviral immunity PRMT1 TBK1
author_facet	Zhenzhen Yan Haifeng Wu Hansen Liu Guimin Zhao Honghai Zhang Wanxin Zhuang Feng Liu Yi Zheng Bingyu Liu Lei Zhang Chengjiang Gao
author_sort	Zhenzhen Yan
title	The protein arginine methyltransferase PRMT1 promotes TBK1 activation through asymmetric arginine methylation
title_short	The protein arginine methyltransferase PRMT1 promotes TBK1 activation through asymmetric arginine methylation
title_full	The protein arginine methyltransferase PRMT1 promotes TBK1 activation through asymmetric arginine methylation
title_fullStr	The protein arginine methyltransferase PRMT1 promotes TBK1 activation through asymmetric arginine methylation
title_full_unstemmed	The protein arginine methyltransferase PRMT1 promotes TBK1 activation through asymmetric arginine methylation
title_sort	protein arginine methyltransferase prmt1 promotes tbk1 activation through asymmetric arginine methylation
publisher	Elsevier
series	Cell Reports
issn	2211-1247
publishDate	2021-09-01
description	Summary: TBK1 is an essential kinase for the innate immune response against viral infection. However, the key molecular mechanisms regulating the TBK1 activation remain elusive. Here, we identify PRMT1, a type I protein arginine methyltransferase, as an essential regulator of TBK1 activation. PRMT1 directly interacts with TBK1 and catalyzes asymmetric methylation of R54, R134, and R228 on TBK1. This modification enhances TBK1 oligomerization after viral infection, which subsequently promotes TBK1 phosphorylation and downstream type I interferon production. More important, myeloid-specific Prmt1 knockout mice are more susceptible to infection with DNA and RNA viruses than Prmt1fl/fl mice. Our findings reveal insights into the molecular regulation of TBK1 activation and demonstrate the essential function of protein arginine methylation in innate antiviral immunity.
topic	protein arginine methylation innate antiviral immunity PRMT1 TBK1
url	http://www.sciencedirect.com/science/article/pii/S2211124721011803
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The protein arginine methyltransferase PRMT1 promotes TBK1 activation through asymmetric arginine methylation

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