Interferon-inducible cytoplasmic lncLrrc55-AS promotes antiviral innate responses by strengthening IRF3 phosphorylation  

作　　者：Yumei Zhou Mengxuan Li Yiquan Xue Zhiqing Li Weitao Wen Xingguang Liu Yuanwu Ma Lianfeng Zhang Zhongyang Shen Xuetao Cao 

机构地区：[1]Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058 Zhejiang, China [2]National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, 200433 Shanghai, China [3]Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China, Institute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, 100021 Beijing, China [4]Department of Liver Transplantation, Tianjin First Center Hospital, Nankai University, 300070 Tianjin, China [5]Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, 100005 Beijing, China [6]College of Life Science, Nankai University, 300071 Tianjin, China

出　　处：《Cell Research》2019年第8期641-654,共14页细胞研究（英文版）

基　　金：We thank Dr. Pin Wang for technical assistance. supported by grants from the National Natural Science Foundation of China (81788101 to X.C.);the National Key Research & Development Program of China (2018YFA0507403 to X.C.);CAMS Innovation Fund for Medical Sciences (2016-12M-1-003 to X.C.).

摘　　要：Type I interferon (IFN-I) production is efficiently induced to ensure a potent innate immune response to viral infection. How this response can be enhanced, however, remains to be explored. Here, we identify a new cytoplasmic long non-coding RNA (lncRNA), lncLrrc55-AS, that drives a positive feedback loop to promote interferon regulatory factor 3 (IRF3) signaling and IFN-I production. We show that lncLrrc55-AS is virus-induced in multiple cell types via the IFN-JAK-STAT pathway. LncLrrc55-AS-deficient mice display a weakened antiviral immune response and are more susceptible to viral challenge. Mechanistically, lncLrrc55-AS binds phosphatase methylesterase 1 (PME-1), and promotes the interaction between PME-1 and the phosphatase PP2A, an inhibitor of IRF3 signaling. LncLrrc55-AS supports PME-1-mediated demethylation and inactivation of PP2A, thereby enhancing IRF3 phosphorylation and signaling. Loss of PME-1 phenocopies lncLrrc55-AS deficiency, leading to diminished IRF3 phosphorylation and IFN-I production. We have identified an IFN-induced lncRNA as a positive regulator of IFN-I production, adding mechanistic insight into lncRNA-mediated regulation of signaling in innate immunity and inflammation.

关 键 词：production POTENT pathway 

分 类 号：Q[生物学]