OAS1 explained

2'-5'-oligoadenylate synthetase 1 is an enzyme that in humans is encoded by the OAS1 gene.^{[1] [2]}

This gene encodes a member of the 2-5A synthetase family, which include essential proteins involved in the innate immune response to viral infection.

The encoded protein is induced by interferons and uses adenosine triphosphate in 2'-specific nucleotidyl transfer reactions to synthesize 2',5'-oligoadenylates (2-5As). These molecules activate latent RNase L, which results in both viral and endogenous RNA degradation and the inhibition of viral replication. The three known members of this gene family are located in a cluster on chromosome 12. Hypomorphic mutations in this gene have been associated with host susceptibility to viral infection, while gain-of-function variants can cause autoinflammatory immunodeficiency.^[3] Alternatively spliced transcript variants encoding different isoforms have been described.^[4]

Further reading

• Justesen J, Hartmann R, Kjeldgaard NO . Gene structure and function of the 2'-5'-oligoadenylate synthetase family . Cellular and Molecular Life Sciences . 57 . 11 . 1593–1612 . October 2000 . 11092454 . 11146851 . 10.1007/PL00000644 . 19154357 . free .
• Ghosh SK, Kusari J, Bandyopadhyay SK, Samanta H, Kumar R, Sen GC . Cloning, sequencing, and expression of two murine 2'-5'-oligoadenylate synthetases. Structure-function relationships . The Journal of Biological Chemistry . 266 . 23 . 15293–15299 . August 1991 . 1651324 . 10.1016/S0021-9258(18)98615-1 . free .
• Silverman RH, Sengupta DN . Translational regulation by HIV leader RNA, TAT, and interferon-inducible enzymes . Journal of Experimental Pathology . 5 . 2 . 69–77 . 1991 . 1708818 .
• Saunders ME, Gewert DR, Tugwell ME, McMahon M, Williams BR . Human 2-5A synthetase: characterization of a novel cDNA and corresponding gene structure . The EMBO Journal . 4 . 7 . 1761–1768 . July 1985 . 2411547 . 554415 . 10.1002/j.1460-2075.1985.tb03848.x .
• Benech P, Mory Y, Revel M, Chebath J . Structure of two forms of the interferon-induced (2'-5') oligo A synthetase of human cells based on cDNAs and gene sequences . The EMBO Journal . 4 . 9 . 2249–2256 . September 1985 . 2416561 . 554493 . 10.1002/j.1460-2075.1985.tb03922.x .
• Williams BR, Saunders ME, Willard HF . Interferon-regulated human 2-5A synthetase gene maps to chromosome 12 . Somatic Cell and Molecular Genetics . 12 . 4 . 403–408 . July 1986 . 2426799 . 10.1007/BF01570735 . 13077134 .
• Hovanessian AG, Laurent AG, Chebath J, Galabru J, Robert N, Svab J . Identification of 69-kd and 100-kd forms of 2-5A synthetase in interferon-treated human cells by specific monoclonal antibodies . The EMBO Journal . 6 . 5 . 1273–1280 . May 1987 . 2440675 . 553929 . 10.1002/j.1460-2075.1987.tb02364.x .
• Rutherford MN, Hannigan GE, Williams BR . Interferon-induced binding of nuclear factors to promoter elements of the 2-5A synthetase gene . The EMBO Journal . 7 . 3 . 751–759 . March 1988 . 2456211 . 454386 . 10.1002/j.1460-2075.1988.tb02872.x .
• Benech P, Vigneron M, Peretz D, Revel M, Chebath J . Interferon-responsive regulatory elements in the promoter of the human 2',5'-oligo(A) synthetase gene . Molecular and Cellular Biology . 7 . 12 . 4498–4504 . December 1987 . 2830497 . 368134 . 10.1128/MCB.7.12.4498 .
• Wathelet MG, Clauss IM, Nols CB, Content J, Huez GA . New inducers revealed by the promoter sequence analysis of two interferon-activated human genes . European Journal of Biochemistry . 169 . 2 . 313–321 . December 1987 . 3121313 . 10.1111/j.1432-1033.1987.tb13614.x . free .
• Wathelet MG, Szpirer J, Nols CB, Clauss IM, De Wit L, Islam MQ, Levan G, Horisberger MA, Content J, Szpirer C . Cloning and chromosomal location of human genes inducible by type I interferon . Somatic Cell and Molecular Genetics . 14 . 5 . 415–426 . September 1988 . 3175763 . 10.1007/BF01534709 . 42406993 .
• Wathelet M, Moutschen S, Cravador A, DeWit L, Defilippi P, Huez G, Content J . Full-length sequence and expression of the 42 kDa 2-5A synthetase induced by human interferon . FEBS Letters . 196 . 1 . 113–120 . February 1986 . 3753689 . 10.1016/0014-5793(86)80224-1 . 38673605 . free . 1986FEBSL.196..113W .
• Shiojiri S, Fukunaga R, Ichii Y, Sokawa Y . Structure and expression of a cloned cDNA for human (2'-5')oligoadenylate synthetase . Journal of Biochemistry . 99 . 5 . 1455–1464 . May 1986 . 3754863 . 10.1093/oxfordjournals.jbchem.a135615 . free .
• Merlin G, Chebath J, Benech P, Metz R, Revel M . Molecular cloning and sequence of partial cDNA for interferon-induced (2'-5')oligo(A) synthetase mRNA from human cells . Proceedings of the National Academy of Sciences of the United States of America . 80 . 16 . 4904–4908 . August 1983 . 6348777 . 384155 . 10.1073/pnas.80.16.4904 . free . 1983PNAS...80.4904M .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Ghosh A, Sarkar SN, Guo W, Bandyopadhyay S, Sen GC . Enzymatic activity of 2'-5'-oligoadenylate synthetase is impaired by specific mutations that affect oligomerization of the protein . The Journal of Biological Chemistry . 272 . 52 . 33220–33226 . December 1997 . 9407111 . 10.1074/jbc.272.52.33220 . free .
• Hovnanian A, Rebouillat D, Mattei MG, Levy ER, Marié I, Monaco AP, Hovanessian AG . The human 2',5'-oligoadenylate synthetase locus is composed of three distinct genes clustered on chromosome 12q24.2 encoding the 100-, 69-, and 40-kDa forms . Genomics . 52 . 3 . 267–277 . September 1998 . 9790745 . 10.1006/geno.1998.5443 .
• Sarkar SN, Ghosh A, Wang HW, Sung SS, Sen GC . The nature of the catalytic domain of 2'-5'-oligoadenylate synthetases . The Journal of Biological Chemistry . 274 . 36 . 25535–25542 . September 1999 . 10464285 . 10.1074/jbc.274.36.25535 . free .

Notes and References

1. Renault B, Hovnanian A, Bryce S, Chang JJ, Lau S, Sakuntabhai A, Monk S, Carter S, Ross CJ, Pang J, Twells R, Chamberlain S, Monaco AP, Strachan T, Kucherlapati R . A sequence-ready physical map of a region of 12q24.1 . Genomics . 45 . 2 . 271–278 . October 1997 . 9344649 . 10.1006/geno.1997.4888 .
2. Nechiporuk T, Nechiporuk A, Sahba S, Figueroa K, Shibata H, Chen XN, Korenberg JR, de Jong P, Pulst SM . A high-resolution PAC and BAC map of the SCA2 region . Genomics . 44 . 3 . 321–329 . September 1997 . 9325053 . 10.1006/geno.1997.4886 .
3. Magg T, Okano T, Koenig LM, Boehmer DF, Schwartz SL, Inoue K, Heimall J, Licciardi F, Ley-Zaporozhan J, Ferdman RM, Caballero-Oteyza A, Park EN, Calderon BM, Dey D, Kanegane H, Cho K, Montin D, Reiter K, Griese M, Albert MH, Rohlfs M, Gray P, Walz C, Conn GL, Sullivan KE, Klein C, Morio T, Hauck F . Heterozygous OAS1 gain-of-function variants cause an autoinflammatory immunodeficiency . Science Immunology . 6 . 60 . eabf9564 . June 2021 . 34145065 . 8392508 . 10.1126/sciimmunol.abf9564 .
4. Web site: Entrez Gene: OAS1 2',5'-oligoadenylate synthetase 1, 40/46kDa .