The human oligoadenylate synthetase (OAS) family consists of four proteins whose production is stimulated by interferon, OAS1, OAS2, OAS3, and OASL. The first three members have the 2'-5'-oligoadenylate synthetase activity for which the family is named (Sadler AJ & Williams BR 2008), whereas OASL is devoid of this activity despite sharing significant sequence similarity with the other OAS proteins (Zhu J et al. 2015). OAS1, 2, and 3 are activated by double-stranded RNA to synthesize 5'-triphosphorylated 2'-5'-oligoadenylates (2-5A) from ATP (Kerr IM & Brown RE 1978). The 2-5A serve as chemically unique second messengers that induce regulated RNA decay by activating ribonuclease L (RNase L), thus mediating antiviral innate immunity (Zhou A et al. 1993; Lin RJ et al. 2009; Huang H et al. 2014; Han Y et al. 2014). RNase L has also been implicated in antibacterial innate immunity (Li XL et al. 2008). RNase L cleaves single-stranded RNA (ssRNA) in U-rich sequences, typically after UU or UA dinucleotides leaving a 5'-OH and 2',3'-cyclic phosphate (Floyd-Smith G et al. 1981; Wreschner DH et al.1981; Cooper DA et al. 2014).

Some OAS proteins have additional or alternative antiviral functions that are independent of RNase L activity (Perelygin AA et al., 2002; Kristiansen H et al. 2011). The precise mechanisms of RNase L-independent OAS antiviral activities remain to be fully elucidated.