Recently, Professor Gao Chengjiang’s group from the School of Basic Medical Sciences of Shandong University published a new paper entitled "The protein arginine methyltransferase PRMT1 promotes TBK1 activation through asymmetric arginine methylation" in Cell Reports. This paper described a novel mechanism for the regulation of TBK1 activation. Ph.D. students Yan Zhenzhen and Wu Haifeng are the co-first authors of this paper. Professor Gao Chengjiang is the corresponding author of this paper.

Innate immunity provides the first line of host defense against invading pathogens. TBK1 serves as an integrator of multiple signal pathways and as a modulator of type I interferon(IFN) signaling. Activated TBK1 directly phosphorylates IFN regulatory factors 3 and 7 (IRF3 and IRF7), promotes their dimerization and nuclear translocation, and then stimulates the production of IFNs. Post-translational modifications (PTMs) play an important role in the regulation of TBK1 activation. Previously, Prof. Gao Chengjiang’s group has identified an E3 ubiquitin ligase RNF128 that promotes the activation of TBK1 through K63-linked ubiquitination (Nature Immunology, 2017). However, other PTMs of TBK1 need further exploration.

Through functional screening of protein arginine methyltransferases (PRMTs) family members, the authors demonstrated that type I protein arginine methyltransferase PRMT1 plays a positive role in the innate antiviral response. Myeloid-specific Prmt1-deficient mice (Prmt1^fl/flLyz2-Cre) are more susceptible to infection with DNA and RNA viruses than Prmt1^fl/flmice. Furthermore, PRMT1 can specifically bind with TBK1 to promote TBK1 arginine methylation, and the methylation level of TBK1 is enhanced upon viral infection. More importantly, they found that methylation mediated by PRMT1 promotes the oligomerization and trans-autophosphorylation of TBK1, which in turn activates the downstream signaling. This study reveals a new PTM of TBK1 and further provides the regulation mechanism of antiviral innate immune response.

Professor Gao Chengjiang’s team has been dedicated to the study of the regulation mechanism of innate immune signal transduction. Multiple research articles have been published in the top-tier journals including Nature Immunology, Journal of Experimental Medicine, Nature Communications, and PLOS Pathogens. This work was supported by the Innovative Research Group Project of Shandong University and the Natural Science Foundation of China. The authors thank Dr. Bao Shilai (Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, China) for providing the Prmt1^fl/flmice.

Link to this paper: https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01180-3