OAS1-gene

The activation of the OAS1 gene occurs through double-stranded RNA (dsRNA). This does not normally occur in a cell. The encoded 2',5'-oligoadenylate synthetase1 is induced by interferons and now generates 2'-5'-linked oligoadenylates from ATP molecules (Koul A et al. 2020). These molecules activate latent RNase L, which causes degradation of both viral and endogenous RNA and inhibition of viral replication. OAS1 continues to play an important role in apoptosis induction.

The 2'-5'-oligoadenylate synthetase1 is a hugely important sensor for cytosolic double-stranded RNA (dsRNA), and thus plays a crucial role in limiting viral infections. Activation of the latent ribonuclease (RNase L) halts viral replication and establishes an antiviral state. The importance of the OAS/RNase L pathway is demonstrated by the fact that different viruses have evolved numerous different strategies to circumvent the effects of OAS activation. How OAS synthetases are regulated by viral or cellular RNAs is not yet fully understood (Schwartz SL et al. 2019).

The 2'-5'-oligoadenylate synthetase 1 (OAS1) plays an important role in infectious immune responses. Mutations in the OAS1 gene have been associated with increased host susceptibility to viral infections. The importance of this enzyme has also been demonstrated for bacterial infections. Thus, OAS1 polymorphisms were found to be associated with increased susceptibility to tuberculosis (Wu S et al. 2018). Significant association with tuberculosis has been demonstrated for the rs10774671 G allele and for the GG genotype (Wu S et al. 2018). In contrast, other OAS polymorphisms (rs1131454 G allele) were TB protective in the Chinese Han population. OAS polymorphisms also appear to play a role in the severity of infection in COVID-19.

Diseases associated with OAS1 include hereditary pulmonary alveolar proteinosis (PAP; Immunodeficiency 100 with Pulmonary Alveolar Proteinosis and Hypogammaglobulinemia, Cho K et al. 2018

A better understanding of the regulation of the OAS gene family may provide a basis for the development of novel antiviral therapeutic strategies and point the way to a deeper understanding of previously ignored cellular functions of the OAS/RNase L pathway in the absence of infection (Schwartz SL et al. 2019).

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