Cell Reports
Volume 36, Issue 12, 21 September 2021, 109731
Journal home page for Cell Reports

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

https://doi.org/10.1016/j.celrep.2021.109731Get rights and content
Under a Creative Commons license
open access

Highlights

  • PRMT1 positively regulates IFN-β signaling in various innate immune signaling pathways

  • Prmt1 knockout mice are more susceptible to viral infection than their counterparts

  • PRMT1 promotes antiviral responses through catalyzing the methylation of TBK1

  • TBK1 methylation is essential for its aggregation and trans-autophosphorylation

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.

Keywords

protein arginine methylation
innate antiviral immunity
PRMT1
TBK1

Data and code availability

All data reported in this paper will be shared by the lead contact upon request. This paper does not report original code. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

2

These authors contributed equally

3

Lead contact