Activation of Oas1a gene expression by type I IFN requires both STAT1 and STAT2 while only STAT2 is required for Oas1b activation.
The murine 2'-5' oligoadenylate synthetase 1a (Oas1a) and Oas1b genes are type 1 IFN responsive genes. Oas1a is an active synthetase with broad antiviral activity mediated through RNase L. Oas1b is inactive but can inhibit Oas1a synthetase activity and mediate a flavivirus-specific antiviral activity through an unknown RNase L-independent mechanism. Analysis of promoter elements regulating gene transcription confirmed that an IFN-stimulated response element (ISRE) is required for IFN beta-activation but neither the overlapping IRF binding site present in both promoters nor the adjacent Oas1b NF-kappa B site is required. Mutation of the overlapping STAT site negatively affected IFN beta-induction of Oas1a but not of Oas1b. Also, IFN beta induction of Oas1a was STAT1- and STAT2-dependent, while induction of Oas1b was STAT1-independent but STAT2-dependent. The two promoters differ at a single nucleotide in the STAT site. The data indicate that these two duplicated genes can be differentially regulated by IFN beta.
Department of Biology, Georgia State University, Atlanta, GA 30302, USA.
Joanna A
JA
Pulit-Penaloza
Svetlana V
SV
Scherbik
Margo A
MA
Brinton
D015088:2',5'-Oligoadenylate Synthetase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015971:Gene Expression Regulation, Enzymologic; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D051379:Mice / Q000235:genetics* / Q000378:metabolism; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020218:Response Elements; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050795:STAT2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase