The exonuclease ISG20 is directly induced by synthetic dsRNA via NF-kappaB and IRF1 activation.
Many interferon (IFN)-stimulated genes are also induced by double-stranded RNA (dsRNA), a component closely associated with the IFN system in the context of virus-host interactions. Recently, we demonstrated that the IFN-induced 3' --> 5' exonuclease ISG20 possesses antiviral activities against RNA viruses. Here we show that ISG20 induction by synthetic dsRNA (pIpC) is stronger and faster than its induction by IFN. Two families of transcription factors are implicated in the transcriptional activation of ISG20 by dsRNA. Initially, the NF-kappaB factors p50 and p65 bind and activate the kappaB element of the Isg20 promoter. This is followed by IRF1 binding to the ISRE. As pIpC often induces protein movements in the cells, we questioned whether it could influence ISG20 localization. Interestingly and contrary to IFN, dsRNA induces a nuclear matrix enrichment of the ISG20 protein. dsRNA induction of ISG20 via NF-kappaB and its antiviral activity led us to suggest that ISG20 could participate in the cellular response to virus infection.
Espert
Lucile
L
CNRS UMR 5160, EFS, 240 avenue Emile Jeanbrau, 34094 Montpellier, Cedex 5, France.
Rey
Clémence
C
Gonzalez
Laure
L
Degols
Geneviève
G
Chelbi-Alix
Mounira Kmar
MK
Mechti
Nadir
N
Gongora
Céline
C
D001665:Binding Sites; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism*; D005095:Exoribonucleases; D006367:HeLa Cells; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012330:RNA, Double-Stranded / Q000138:chemical synthesis / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I; D016328:NF-kappa B; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012330:RNA, Double-Stranded; D014157:Transcription Factors; D005092:Exonucleases; D005095:Exoribonucleases; C112346:ISG20 protein, human