Disease relevance of OAS1

• The study was carried out to investigate the association between the genetic polymorphisms of 2',5'-oligoadenylate synthetase 1 (OAS1) gene as well as myxovirus resistance 1 (MxA) gene and susceptibility to SARS in Chinese Han population [1].
• Single nucleotide polymorphisms in genes for 2'-5'-oligoadenylate synthetase and RNase L inpatients hospitalized with West Nile virus infection [2].
• Vaccinia virus E3L protein is an inhibitor of the interferon (i.f.n.)-induced 2-5A synthetase enzyme [3].
• Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR [4].
• Studies of interferon (IFN)-treated virus-infected animal cells have revealed the 2-5A system (2-5A synthetase/RNase L enzymes) as being responsible for virus inhibition only in the case of picornaviridae [5].

Psychiatry related information on OAS1

• mRNA levels and methylation patterns of the 2-5A synthetase gene in control and Alzheimer's disease (AD) fibroblasts [6].

High impact information on OAS1

• This crystal structure of a 2'-5'-oligoadenylate synthetase reveals a structural conservation with the 3'-specific poly(A) polymerase that, coupled with structure-guided mutagenesis, supports a conserved catalytic mechanism for the 2'- and 3'-specific nucleotidyl transferases [7].
• Analysis of the kinetics of cytokine mRNA production showed that levels fall shortly after the rise of 2-5A synthetase mRNA [8].
• IFN-beta ser was more effective than IFN-gamma in enhancing 2-5A synthetase activity (P = 0.001) [9].
• This was consistent with elevated levels of serum acid-labile IFN alpha and cellular 2-5A synthetase activity in patients [10].
• The time course of induction excluded, however, that the decrease of c-myc RNA is caused by induction of the 2-5A synthetase/RNase L endonuclease system [11].

Chemical compound and disease context of OAS1

• This synergism was also observed for the induction of 2'-5'-oligoadenylate-synthetase, an enzyme which is not expressed constitutively on BT-20 human breast cancer cells and not inducible by retinoic acid or TNF-alpha alone [12].
• This retrospective study was aimed at assessing whether 2-5AS activity functions as a clinical marker of virological response to PEG-interferon-alpha2b (PEG-IFN) plus ribavirin therapy of chronic hepatitis C [13].
• Enhancement of natural killer cell activity and 2-5A synthetase in operable breast cancer patients treated with polyadenylic; polyuridylic acid [14].
• Ampligen treatment of renal cell carcinoma: changes in 2-5A synthetase, 2-5A oligomer size and natural killer cell activity associated with antitumor response clinically [15].

Biological context of OAS1

• Significant association was detected at multiple markers, the strongest being at an A/G single-nucleotide polymorphism at the exon 7 splice-acceptor site (AG or AA) of the OAS1 gene [16].
• This genetic polymorphism makes OAS1 an excellent candidate for a human gene that influences host susceptibility to viral infection [16].
• Calculations using the nonparametric Kolmogorov-Smirnov test suggested that the homogenization of paralogous OAS1 sequences was due to gene conversion rather than stabilizing selection [17].
• By in situ hybridization, we assign the human OAS-40/46, OAS-69/71, and OAS-100 genes (referred to as OAS1, OAS2, and OAS3, respectively) to a unique cytogenetic location on chromosomal region 12q24 [18].
• The associations of AG genotype in OAS1 and GT genotype in MxA remained significant in multivariate analyses after adjusting for SARS protective measures (OR = 0.38, 95% CI: 0.14-0.98 and OR = 3.22, 95% CI: 1.13-9.18, respectively) [1].

Anatomical context of OAS1

• Using cloned probes on Southern blots of DNA from a panel of rodent-human somatic cell hybrids, we have assigned the IFI-4 gene to chromosome 1 and the gene coding for the low-molecular-weight 2-5A synthetase to chromosome 12 [19].
• The enzyme 2-5A synthetase is induced in cultured cells in response to interferon (IFN) treatment [20].
• When this capped RNA was introduced by microinjection into Xenopus oocytes, production of 2-5A synthetase was clearly observed in the cytoplasm and 10-30% of the enzyme accumulated with time in the nucleoplasm [21].
• When the cDNA was expressed in COS-7 cells with an eukaryotic promoter, active 2-5A synthetase was produced and localized mainly in the cytoplasm [22].
• Immune interferon inhibits proliferation and induces 2'-5'-oligoadenylate synthetase gene expression in human vascular smooth muscle cells [23].

Associations of OAS1 with chemical compounds

• Variation in antiviral 2',5'-oligoadenylate synthetase (2'5'AS) enzyme activity is controlled by a single-nucleotide polymorphism at a splice-acceptor site in the OAS1 gene [16].
• A serine/glycine substitution in OAS1 exon 3 is more likely a functional variant [24].
• 2'-5'-Oligoadenylate synthetase, serum beta 2-microglobulin, neopterin, and p78 levels all increased significantly, and serum tryptophan decreased significantly within 24 h after the initiation of treatment (P less than 0.0001) [25].
• In addition, we demonstrate that ISF21 is necessary for transcriptional activation of 2'-5'-oligoadenylate synthetase, 6-16, and guanylate-binding protein gene promoter reporter constructs, which are mediated by several signaling pathways [26].
• The increase in serum beta2-microglobulin, neopterin and 2-5A-synthetase was more sustained [27].

Physical interactions of OAS1

• The cells were returned to monolayer growth for 18 h, and then harvested and assayed to determine the amount of RNase L protein (via [32P]2-5A binding) and the specific activities of RNase L and 2-5A synthetase [28].

Regulatory relationships of OAS1

• Lymphoblastoid Raji cells were insensitive to the antiviral and anticellular activities of IFN-alpha, beta and gamma, but 2-5A synthetase was induced in cells by the treatment with IFN-alpha and beta, though the enzyme level was lower than that found in interferon-treated Daudi cells [29].
• We hypothesized that polymorphisms in the OAS1 gene could influence the susceptibility to MS [30].
• 2-5A synthetase activity was significantly enhanced when the cells were treated with doses of TNF that afforded antiviral protection [31].

Other interactions of OAS1

• Susceptibility to WNV disease in inbred strains of mice was mapped to a nonsense mutation in the gene encoding the 1b isoform of 2'-5'-oligoadenylate synthetase (OAS), a member of the OAS/RNase L system of innate viral resistance [2].
• OAS1 is the small form and OAS2 is the medium form of the human interferon-induced 2'-5' oligoadenylate synthetases [32].
• At days 7 and 28, induction of OAS1, IFI44 and IRF7 showed significant pair-wise correlation in individual patients (r>0.7 and P<0.001) [33].
• In the present study, we genotyped 835 type 1 diabetic and 401 healthy siblings at the OAS1 splice site polymorphism and (for comparison) at an A/C SNP of the insulin (IDDM2) locus [34].
• End point real time polymerase chain reaction (PCR) and PCR-based Restriction Fragment Length Polymorphism (RFLP) analysis were used to detect the single nucleic polymorphisms (SNPs) in OAS1 and MxA genes [1].

Analytical, diagnostic and therapeutic context of OAS1

• MATERIAL/METHODS: Using a novel conjunction of comparative modeling, molecular surface analysis, and sequence analysis, high-resolution models of the known isoforms of human OAS1 were prepared [35].
• Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes: a case-control study [1].
• Cytotoxicity or OAS1 induction could be reduced by changing shRNA sequence or vector titre, but stable gene silencing could not be maintained in extended cell culture despite persistent marker gene expression from the RNAi-inducing transgene cassette [36].
• RNA drug therapy acting via the 2-5A synthetase/RNase L pathway [37].
• 2-5A synthetase levels were twofold higher in B than in T lymphocytes separated by fluorescence-activated cell sorting [38].

References