2'-5'-oligoadenylate synthetase-like protein (OASL)

2'-5'-oligoadenylate synthetase-like protein (OASL) is an interferon-inducible enzyme related to the OAS family, predominantly expressed in response to viral infection via IFN signaling[3][4]. While canonical OAS proteins catalyze the synthesis of 2'-5'-linked oligoadenylates that activate RNase L to degrade viral and cellular RNA, human OASL has lost synthetase activity due to changes in its active site[1][3][4]. Instead, OASL contains ubiquitin-like domains at its C-terminus that allow it to mimic polyubiquitin and bind directly to the RIG-I viral RNA sensor, enhancing RIG-I's capacity to induce type I interferons and restrict RNA virus replication[2][3][4]. In DNA virus infection, OASL can inhibit the DNA sensor cGAS, dampening IFN production[1]. OASL is highly dynamic, being upregulated not only by various viruses but also by intracellular pathogenic bacteria, modulating autophagy and antimicrobial peptide secretion and influencing host-pathogen interactions[1]. Variants and polymorphisms in OASL are associated with susceptibility to several viral diseases[3]. There is no evidence of small molecule drugs directly targeting OASL, though its regulation by interferons is therapeutically relevant[4]. OASL is a promising target for modulating innate immunity but poses complexities due to its context-dependent pro- and anti-viral effects[1][2][3][4][5].

Other names

2'-5'-oligoadenylate synthase-like proteinOASLTRIP142'-5'-OAS-RPthyroid receptor-interacting protein 14p59 OASLOASL12'-5'-OAS-related protein59 kDa 2'-5'-oligoadenylate synthetase-like proteinOASLdOASLaOASLb

For its biological role: Acts as a viral RNA sensor co-factor, enhancing RIG-I-mediated interferon response (by mimicking polyubiquitin). Binds to cytosolic DNA sensor cGAS, inhibiting its activity and interferon signaling (pro-viral role in some DNA virus infections). Upregulated by interferons via IRF3 signaling. Involved in OAS/RNase L pathway activation in avian species.