Recently, professor Han Lihui's team in School of Basic Medical Sciences of Shandong University has made new contribution in the field of innate immune regulation, and published a research paper entitled "arginine methyltransferase PRMT5 negatively regulates cGAS-mediated antiviral immune response" online in Science Advances (five years’ IF=14.094). Professor Han Lihui in Department of Immunology, Shandong University School of Basic Medical Sciences, is the corresponding author. Ph.D candidate Ma Dapeng is the first author, and Shandong University is the first author institute and the sole corresponding author institute.
The innate immune system is the first line of defense against the invasion of external pathogens and the occurrence of tumors. Cyclic GMP-AMP synthase (cGAS) was firstly identified as an intracellular DNA sensor in 2013, and it could sense the cytoplasmic DNA produced by virus or other pathogens and further fight against the pathogens by initiating innate immune response. The effective activation of cGAS is an important immune defense strategy; however excessive activation results in severe inflammation, even autoimmune diseases. Therefore, the activation of cGAS must be tightly regulated to ensure its effect of immune defense without further autoimmune injury. The post-translational modification of cGAS is recognized as an important strategy for precise regulation of its activity. Arginine methylation is an important post-translational modification involved in the regulation of many biological processes. However, whether cGAS could be modified by arginine methylation remains to be clarified.
Through high throughput screening, professor Han Lihui's group found that PRMT5 was a bona fide binding partner of cGAS, and it could catalyze the symmetrical dimethylation of arginine at Arg124 site in N terminal region of cGAS. This modification directly inhibits the DNA-binding ability of cGAS, and exerts negative regulatory effect on the antiviral innate immune response mediated by cGAS. The methylation modification of cGAS by PRMT5 is an important strategy of innate immune regulation. In quiescent cells, PRMT5 directly interacts with cGAS and methylates cGAS at Arg124 residue, which helps to prevent cGAS from binding to self DNA and maintain the immune homeostasis. Upon virus infection, PRMT5 gradually dissociates from cGAS and restores the DNA-binding ability of cGAS, which facilities cGAS to sense viral DNA and initiate antiviral immune response. This study provides a foundation for the thorough elucidation of the regulatory mechanism of innate immunity, and provides a novel target therapeutic strategy for the regulation of cGAS-involved processes, included antiviral immunity, tumor immunity and autoimmunity.
Professor Han Lihui's academic team entitled "Immune Microenvironment and Tumors" has gradually condensed into stable research directions since its establishment. In recent three years, great progress has been made in tumor immunity and natural immune regulation. Several patents have been authorized by the State Intellectual Property Office, and the research papers with professor hanlihui as independent corresponding author have been published in a series of international mainstream journals, including Oncogene (2018), Cell death and Differentiation (2020), and Science Advances (2021). The research paper published in Oncogene (2018) has been indexed as high cited papers by ESI system. The above research work has been funded by the National Natural Science Foundation of China.
Written by：Ma Dapeng