OAS1-gene

OAS1 is the acronym for "2'-5'-oligoadenylate synthetase 1" and refers to a gene belonging to the OAS gene family. This oligoadenylate synthetase gene family consists of a cluster of four genes: OAS1, OAS2, OAS3 and OASL. Except for OASL (OAS like protein), their gene products have 2'5' OAS enzyme activities (Rebouillat D et al. 1999).

The genes OAS1, OAS2 and OAS3 are encoded by a tightly linked locus on 12q24.1. The additional member of the human OAS family, the OASL gene, is located on 12q24.2. The OAS1 gene encodes five isoforms of oligoadenylate synthetases (p42, p44, p46, p48 and p52) (Rebouillat D et al. 1998). A total of 11 different oligoadenylate synthetase isoforms are encoded in the OAS gene cluster by alternative splicing. The OASL protein (OAS-like protein) has no 2'5' OAS activities (Rebouillat D et al. 1999).

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).

1. Bonella F et al (2011) Pulmonary alveolar proteinosis: new insights from a single-center cohort of 70 patients. Respir Med 105:1908-1916.

2. Campo I et al (2013) Assessment and management of pulmonary alveolar proteinosis in a reference center. Orphanet J Rare Dis 8:40.

3. Carpten J et al (2002) Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nature Genet 30: 181-184
4. Cher M L et al (1996) Genetic alterations in untreated metastases and androgen-independent prostate cancer detected by comparative genomic hybridization and allelotyping. Cancer Res 56: 3091-3102
5. Elkhateeb E et al (2016) The role of mouse 2',5'-oligoadenylate synthetase 1 paralogs. Infect Genet Evol. 45:393-401.
6. Hovanessian AG et al. (2007) The human 2'-5'oligoadenylate synthetase family: unique interferon-inducible enzymes catalyzing 2'-5' 7instead of 3'-5' phosphodiester bond formation. Biochimie 89:779-788.
7. Koul A et al. (2020) Impact of double-stranded RNA characteristics on the activation of human 2'-5'-oligoadenylate synthetase 2 (OAS2). Biochem Cell Biol 98:70-82.
8. Rebouillat D et al. (1999) The human 2',5'-oligoadenylate synthetase family: interferon-induced proteins with unique enzymatic properties. J Interferon Cytokine Res 19: 295-308.
9. Schwartz SL et al (2019) RNA regulation of the antiviral protein 2'-5'-oligoadenylate synthetase. Wiley Interdiscip Rev RNA. 10: e1534.
10. Wu S et al. (2018) 2'-5'-oligoadenylate synthetase 1 polymorphisms are associated with tuberculosis: a case-control study. BMC Pulm Med 18:180.