Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.
PLoS Pathog
; 17(9): e1009918, 2021 09.
Article
in English
| MEDLINE | ID: covidwho-1622376
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA Virus Infections
/
Gene Expression Regulation
/
Receptors, Cell Surface
/
Histone Demethylases
Limits:
Animals
/
Humans
Language:
English
Journal:
PLoS Pathog
Year:
2021
Document Type:
Article
Affiliation country:
Journal.ppat.1009918
Similar
MEDLINE
...
LILACS
LIS