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

Zhenzhen Yan; Haifeng Wu; Hansen Liu; Guimin Zhao; Honghai Zhang; Wanxin Zhuang; Feng Liu; Yi Zheng; Bingyu Liu; Lei Zhang; Chengjiang Gao

Cell Reports (Sep 2021)

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

Zhenzhen Yan,
Haifeng Wu,
Hansen Liu,
Guimin Zhao,
Honghai Zhang,
Wanxin Zhuang,
Feng Liu,
Yi Zheng,
Bingyu Liu,
Lei Zhang,
Chengjiang Gao

Affiliations

Zhenzhen Yan: Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
Haifeng Wu: Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
Hansen Liu: Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
Guimin Zhao: Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
Honghai Zhang: Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
Wanxin Zhuang: Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
Feng Liu: Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
Yi Zheng: Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
Bingyu Liu: Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
Lei Zhang: Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
Chengjiang Gao: Key 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 author

Journal volume & issue: Vol. 36, no. 12
p. 109731

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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