Targeting PRMT7-mediated monomethylation of MAVS enhances antiviral innate immune responses and inhibits RNA virus replication

• 成果类型: Article
• 署名作者: Yang, Jingjing; Li, Wenjuan; Zhang, Zepeng; Gong, Xiaohua; Chen, Yanchao; Peng, Xiaoyu; Hu, Guosheng; Dai, Xianglong; He, Yaohui; Huang, Ying; Cao, Shiqiang; Yang, Yang; Liu, Wen
• 署名单位: Xiamen University; Southern University of Science & Technology; Xiamen University; Fujian Medical University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13641
• DOI: 10.1073/pnas.2408117121
• 发表日期: 2024-11-19
• 关键词: rig-i; signaling protein; arginine methylation; structural basis; RECOGNITION; receptors; activate; cleaves

摘要

RIG- I- like receptors (RLRs)- mitochondrial antiviral signaling protein (MAVS) are crucial for type I interferon (IFN) signaling pathway and innate immune responses triggered by RNA viruses. However, the regulatory molecular mechanisms underlying RNA virus- activated type I IFN signaling pathway remain incompletely understood. Here, we found that protein arginine methyltransferase 7 (PRMT7) serves as a negative regulator of the type I IFN signaling pathway by interacting with MAVS and catalyzing the downregulation and dissociation of PRMT7 from MAVS as well as the decrease of I IFN signaling activation, and antiviral immune responses. Knock- in mice with MAVS Virus infection due to enhanced antiviral immune responses. PiPRMT7- MAVS, a short peptide inhibitor designed to interrupt the interaction between PRMT7 and promoting MAVS aggregation, activating type I IFN signaling, and bolstering antiviral immune responses to suppress RNA virus replication. Moreover, the clinical relevance of PRMT7 is highlighted that it is significantly downregulated in RNA virus- infected clinical samples, such as blood samples from severe acute respiratory syndrome coronavirus Our findings uncovered that PRMT7- mediated arginine methylation plays critical roles in regulating MAVS- mediated antiviral innate immune responses, and targeting arginine methylation might represent a therapeutic avenue for treating RNA viral infection.