Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.
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.
Mesh Terms:
Animals, Chlorocebus aethiops, Gene Expression Regulation, HEK293 Cells, Histone Demethylases, Humans, Mice, Mice, Inbred C57BL, RNA Virus Infections, Receptors, Cell Surface, Ubiquitination, Vero Cells
Animals, Chlorocebus aethiops, Gene Expression Regulation, HEK293 Cells, Histone Demethylases, Humans, Mice, Mice, Inbred C57BL, RNA Virus Infections, Receptors, Cell Surface, Ubiquitination, Vero Cells
PLoS Pathog
Date: Dec. 01, 2020
PubMed ID: 34529741
View in: Pubmed Google Scholar
Download Curated Data For This Publication
234065
Switch View:
- Interactions 6