Prof. Xuetao Cao’s Group Published New Regulatory Mechanism For Interferon Antiviral Function


Prof. Xuetao Cao (Peking Union Medical College, Chinese Academy of Medical Sciences) and his group published a research article in Nature Immunology about the inhibiting mechanism of RNF2 on interferon function (Liu S, Jiang M, Wang W, Liu W, Song X, Ma Z, Zhang S, Liu Y & Cao X. Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA. Nat Immunol 19, 41-52 (2018).).

Supported by the grants from National Natural Science Foundation of China, National Key Basic Research Program of China and the CAMS Innovation Fund for Medical Sciences, Prof. Xuetao Cao, PhD student Shuo Liu and associate professor Minghong Jiang screened the regulatory function of RNF family in antiviral immune responses. They demonstrated that E3 ligase RNF2 increased the K33-linked polyubiquitination on K379 of STAT1, by which promoted STAT1 disassociation from DNA and ultimately inhibited the expression of ISGs. They found that multiple members of RNF family could participate in the regulation of antiviral responses, however, epigenetic regulator RNF2 inhibited STAT1-mediated ISGs transcription independent of its regulation on chromatin and histones. Myeloid-cell-specific RNF2-deficient mice showed enhanced resistance and increased ISGs expression in response to multiple viral infection, which further suggesting the negative regulating role of RNF2 on type I interferon signaling and antiviral responses.

This work deepens the knowledge on the regulatory mechanism of antiviral responses, providing new treatment strategy and potential drug target for viral infection and the relative inflammatory diseases.