Genomic Structure of the Mouse 2',5'-Oligoadenylate Synthetase Gene Family

Abstract

2′,5′-Oligoadenylate synthetase (2-5OAS) is one of the interferon (IFN)-induced proteins and mediates the antiviral action of IFN. In human, three classes of 2-5OAS genes (OAS1, OAS2, and OAS3) and one OAS-like gene (OASL) are reported. In mice, however, OAS genes corresponding to human OAS2 and OAS3 have not been identified. In this report, we identified six novel OAS family genes in mice by screening mouse genomic library and expressed sequence tag (EST) database. These genes include three homologs of the human OAS1 and each homologous gene of the human OAS2,OAS3, and OASL, respectively. Each gene displays 52%-65% amino acid identity to the corresponding human homologs. Nine 2-5OAS genes, except for two OASL genes, locate within the 210-kb genomic region and form a cluster. Each novel 2-5OAS gene showed a characteristic expression pattern among different tissues, and all of them were induced by polyinosinic-polycytidylic acid. Biochemical analyses using recombinant proteins produced in Escherichia coli showed that all the novel mouse 2-5OAS molecules have double-stranded RNA (dsRNA) binding ability, but they do not have 2-5OAS activity except for the OAS2 and OAS3 mouse homologs. These results show that there are at least 11 OAS genes, which are classified into four groups, in the mouse.