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.

► 5′ STAT and 3′ IRF binding sites overlap the Oas1a and Oas1b ISREs.
► The overlapping IRF binding sites are not required for gene induction by IFN beta.
► The ISRE and STAT sites are required for IFN beta induction of Oas1a.
► The ISRE but not the STAT site is required for IFN beta induction of Oas1b.
► Oas1a requires STAT1 and STAT2 while Oas1b needs only STAT2 for IFN beta induction.