Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression

• Published in: PLoS pathogens Vol. 17; no. 9; p. e1009918
• Main Authors: Hu, Qi-Xin, Wang, Hui-Yi, Jiang, Lu, Wang, Chen-Yu, Ju, Lin-Gao, Zhu, Yuan, Zhong, Bo, Wu, Min, Wang, Zhen, Li, Lian-Yun
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 16.09.2021; Public Library of Science (PLoS)
• Subjects: Antibodies; Antiviral agents; Biology and Life Sciences; Bone marrow; Calcium phosphates; Development and progression; Gene expression; Genetic aspects; Histones; Infections; Interferon; Kinases; Laboratory animals; Life sciences; Lungs; Medicine and Health Sciences; Pathogens; Pattern recognition; Penicillin; Phosphorylation; Physical Sciences; Proteins; Research and Analysis Methods; Retinoic acid; Ribonucleic acid; RNA; RNA virus infections; RNA viruses; Signal transduction; Signaling; siRNA; Ubiquitin-proteasome system; Ubiquitination; Virus research; Viruses; China
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1009918

Under RNA virus infection, retinoic acid-inducible gene I (RIG-I) in host cells recognizes viral RNA and activates the expression of type I IFN. To investigate the roles of protein methyltransferases and demethylases in RIG-I antiviral signaling pathway, we screened all the known related enzymes with a siRNA library and identified LSD1 as a positive regulator for RIG-I signaling. Exogenous expression of LSD1 enhances RIG-I signaling activated by virus stimulation, whereas its deficiency restricts it. LSD1 interacts with RIG-I, promotes its K63-linked polyubiquitination and interaction with VISA/MAVS. Interestingly, LSD1 exerts its function in antiviral response not dependent on its demethylase activity but through enhancing the interaction between RIG-I with E3 ligases, especially TRIM25. Furthermore, we provide in vivo evidence that LSD1 increases antiviral gene expression and inhibits viral replication. Taken together, our findings demonstrate that LSD1 is a positive regulator of signaling pathway triggered by RNA-virus through mediating RIG-I polyubiquitination.