The Nutrition and Health Institute has discovered a new mechanism for TRIM24 in antiviral immunity.

On April 23, the international academic journal Journal of empirical medicine published online the research paper "trim24 facilities anti infection through mediating k63 linked traf3 ubiquitation" by Xiao Yichuan, Key Laboratory of tumor and microenvironment, Shanghai Institute of nutrition and health, Chinese Academy of Sciences.this study revealed that trim24 directly promoted the ubiquitination of the k63 linkage of traf3, and then affected the antiviral immunity in vivo, which provided a new molecular target for the regulation of antiviral immunity.RNA virus infection has been a serious threat to people's health.when RNA virus infects the host, the RNA of the virus is recognized by the related pattern recognition receptor rig-i. then Mavs is recruited and a series of signal transduction are carried out to produce type I interferon and proinflammatory factors to inhibit the invasion of the virus.however, the specific mechanism of host antiviral immune response is still unclear.ubiquitination is a common type of post-translational modification, and several articles have reported the important role of ubiquitination in antiviral immunity.in this study, 49 ubiquitination regulatory genes with significant differences in expression after infection with VSV were identified by high-throughput transcriptome sequencing (RNA SEQ). Then, siRNAs were used to interfere the expression of these genes to investigate whether these ubiquitination regulatory genes play an important role in anti viral infection.the E3 ubiquitin ligase trim24, a kind of trim family protein, was screened out, which could significantly increase the expression of interferon type I and reduce the virus titer in infected cells.in vivo experiments also showed that trim24 had a strong antiviral effect.the following studies found that trim24 could be transferred from the nucleus to the cytoplasm under the guidance of CRM1 protein after VSV infection, and finally aggregated on the mitochondria.subsequently, trim24 and traf3 were Co located, which mediated the ubiquitination of k63 at the k429 / k436 site of traf3 protein, promoted the binding of traf3 with Mavs and tbk1, and then promoted the activation of IRF3 and enhanced the expression of ifn-i.subsequently, the researchers continued to explore the mechanism of trim24 regulated by RNA virus infection, and found that the activated IRF3 could directly bind to the promoter region of trim24 gene, resulting in transcriptional inhibition of trim24 gene, and eventually leading to the decrease of trim24 protein expression, which led to the down regulation of interferon type I in the later stage of virus infection, thus avoiding long-term immune hyperactivity To change.this study for the first time shows that trim24 plays an important role in antiviral immunity, so targeted trim24 can be used as a potential molecular target for antiviral immune intervention.Xiao Yichuan, a researcher at the Institute of nutrition and health, is the corresponding author of the paper, and Zhu Chenchen, a doctoral candidate, is the first author.the work was supported by Qin Jun, a researcher at the Institute of nutrition and health, Hou fajian, a researcher at the Institute of Biochemistry and cell biology, Chinese Academy of Sciences, and Wu Xuefeng, a researcher at Shanghai Institute of immunology, School of Medicine, Shanghai Jiaotong University.the research was also supported by the Ministry of science and technology, the National Natural Science Foundation of China and the Chinese Academy of Sciences, as well as the public technology platform and animal platform of the Institute of nutrition and health.the new mechanism of trim24 in antiviral immunity discovered by nutrition and health