Characterization of the gene encoding the 100-kDa form of human 2 ',5 ' Oligoadenylate synthetase

The 2'-5' oligoadenylate synthetases (OAS) represent a family of interferon (IFN)-induced proteins implicated in the antiviral action of IFN. When act ivated by double-stranded (ds) RNA, these proteins polymerize ATP into 2'-5 ' linked oligomers with the general formula pppA(2'p5'A)n, n greater than o r equal to 1. Three forms of human OAS have been described corresponding to proteins of 40/46, 69/71, and 100 kDa. These isoforms are encoded by three distinct genes clustered on chromosome 12 and exhibit differential constit utive and IFN-inducible expression. Here we describe the structural and fun ctional analysis of the gene encoding the large form of human GAS. This gen e has 16 exons with exon/intron boundaries that are conserved among the dif ferent isoforms of the human OAS family, reflecting the evolutionary link a mong them. The promoter region of the p100 gene is composed of multiple fea tures conferring direct inducibility not only by IFNs but also by TNF and a ll-trans retinoic acid. In contrast, the induction of the p100 promoter by dsRNA is indirect and requires IFN type I production. (C) 2000 Academic Pre ss.