TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response.
Virus infection induces host antiviral responses including induction of type I IFNs. Transcription factor IFN regulatory factor 3 (IRF3) plays an essential role and is tightly regulated in this process. Herein we report that TRIM21 (tripartite motif-containing 21) is significantly induced and interacts with IRF3 upon RNA virus infection. Ectopic expression or knockdown of TRIM21 could respectively enhance or impair IRF3-mediated gene expression. Mechanistically, TRIM21 interferes with the interaction between Pin1 (peptidyl-prolyl cis/trans isomerase, NIMA-interacting 1) and IRF3, thus preventing IRF3 ubiquitination and degradation. A conserved motif in the B 30.2 domain of TRIM21 is critical for its modulation of IRF3 function, while the RING finger is dispensable. Host antiviral responses are significantly boosted or crippled in the presence or absence of TRIM21. Our results identify TRIM21 as an essential modulator of IRF3 stability and demonstrate that it positively regulates the strength and duration of primary antiviral response, thus further strengthening the notion that the TRIM family is evolutionarily integrated with innate immunity.
Yang
Kai
K
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Shi
He-Xin
HX
Liu
Xin-Yi
XY
Shan
Yu-Fei
YF
Wei
Bo
B
Chen
She
S
Wang
Chen
C
D000998:Antiviral Agents / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019143:Evolution, Molecular; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000502:physiology; D010253:Respirovirus Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D012261:Ribonucleoproteins; D029082:Sendai virus / Q000276:immunology; D054875:Ubiquitination / Q000276:immunology; D000099207:SS-A Antigen
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C494232:IRF3 protein, human