OAS1 Human

2’-5’ Oligoadenylate Synthetase 1 (OAS1) is a crucial enzyme in the human innate immune response. It is part of the 2’-5’ oligoadenylate synthetase family, which is induced by interferons and plays a significant role in antiviral defense mechanisms .

OAS1 is an interferon-induced enzyme that uses adenosine triphosphate (ATP) to synthesize 2’-5’ oligoadenylates (2-5As) through 2’-specific nucleotidyl transfer reactions . These 2-5As molecules activate latent RNase L, leading to the degradation of viral RNA and inhibition of viral replication . The enzyme consists of two double-stranded RNA (dsRNA)-binding sites located approximately 30 Å apart, which are essential for its antiviral activity .

The OAS1 gene is located on chromosome 12 and is part of a cluster of related genes . Alternative splicing of this gene results in multiple transcript variants with different enzymatic activities . Polymorphisms in the OAS1 gene have been associated with susceptibility to viral infections, including SARS-CoV-2, and type 1 diabetes mellitus .

OAS1 plays a critical role in the cellular innate antiviral response. Upon activation by interferons, OAS1 synthesizes 2-5As, which in turn activate RNase L. This activation leads to the degradation of viral RNA, effectively inhibiting viral replication . The enzyme has been shown to potently inhibit the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic .

Recent research has highlighted the importance of OAS1 in antiviral defense. For instance, a study demonstrated that the prenylated form of human OAS1 could block SARS-CoV-2 replication . This finding underscores the potential therapeutic applications of OAS1 in treating viral infections. Additionally, the enzyme’s role in other cellular processes such as apoptosis, cell growth, differentiation, and gene regulation has been explored .