Recently, professor Gao Chengjiang’s team in the School of Basic Medical Sciences of Shandong University published a new paper titled "The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation" in Nature communications (IF:17.694). PhD student Bai Xuemei is the first author of the paper. Professor Gao Chengjiang and researcher Liu Bingyu of Shandong University are the co-corresponding authors. Shandong University is the first author institute and the sole corresponding author institute.

Innate immunity provides the first line of defence against pathogen invasion. The mitochondrial antiviral signaling protein (MAVS, also known as IPS-I / VISA / CARDIF) is a key adapter protein of innate immune signaling pathway. The signaling adaptor MAVS forms prion-like aggregates to activate the innate antiviral immune response after viral infection. Aggregation of MAVS further induces the activation of the TANK-binding kinase 1 (TBK1) and cytosolic kinases IKK, which then activate the transcription factors IRF3 and NF-κB and result in the production of type-I IFNs and pro-inflammatory cytokines to defend against viral proliferation. As indicated by a number of existing studies, MAVS is the key adapter protein of RLRs to defend against RNA viruses. Additionally, spontaneous aggregation of MAVS has been reported to be associated with autoimmune diseases. Hence, efficient activation of MAVS is crucial for mediating the host innate immunity against viral infection and must be tightly regulated to avoid potentially harmful tissue damage. However, the molecular mechanism that inhibits the spontaneous aggregation of MAVS in quiescent cells remains unclear.

In this study, we reported that protein arginine methyltransferase PRMT9 is a negative regulator of innate antiviral immunity. PRMT9 deficiency enhanced the innate antiviral response to RNA viruses both in vitro and in vivo. Here we reported that PRMT9 targets MAVS directly and catalyzes the arginine methylation of MAVS at the Arg41 and Arg43. In the resting state, this modification inhibited MAVS aggregation and autoactivation of MAVS. Upon virus infection, PRMT9 was dissociated from the mitochondria, leading to the aggregation and activation of MAVS. Our study unveiled a new form of post-translational modification (PTM) on MAVS, which could keep MAVS inactive.

Prof. Gao Chengjiang’s team has long been committed to the research of the regulation mechanism of innate immune signal transduction, and systematically exploring the regulation mechanism of anti-viral innate immune signal transduction and inflammatory response. A number of research articles have been published in Nature Immunology, Nature Communications, Advanced Science, Signal Transduction and Targeted Therapy, Journal of Experimental Medicine, Cell Death & Differentiation, PLOS Pathogens, Journal of Immunology and other international authoritative journals. This work was supported by the Innovative Research Group Project of Shandong University. This work was also supported by the Natural Science Foundation of China and the Postdoctoral Science Foundation of China.

Link to this paper: https://www.nature.com/articles/s41467-022-32628-