OASL explained

59 kDa 2'-5'-oligoadenylate synthetase-like protein is an enzyme that in humans is encoded by the OASL gene.^{[1] [2]}

2'-5'-oligoadenylate synthase is a protein family of structurally similar proteins, including OAS1, OAS2, and OAS3. However, mutations in the OAS domain mean it lacks the motif to allow oligomerization, preventing the synthesis of oligoadenylates. OASL, like the proteins of 2'-5'-oligoadenylate synthase family, is induced by interferons.

Function

RNA Virus Infection

In RNA virus infection, viral genetic material binds to the RNA sensor RIG-I, triggering a reaction cascade that culminates in the secretion of type I interferons.^[3] OASL acts as a sensitiser of RIG-I, binding to the caspase activation and recruitment domain and enhancing interferon production.^[4]

DNA Virus Infection

While OASL has an anti-viral role in RNA viral infection, it has also demonstrated a pro-viral role in DNA viral infection.^[5] OASL can bind to the viral DNA sensor cGAS, inhibiting its catalytic activity and preventing the secretion of interferons.^[6]

Intracellular Bacterial Infection

OASL is shown to be upregulated during a wide variety of vacuolar and cytosolic bacterial infections.^[7] It possesses an ability to inhibit autophagic mechanisms and antimicrobial peptide secretion within the host cell through unclear mechanisms, preventing clearance of the pathogen and creating a favourable intracellular environment.^[8]

See also

• Oasl2, a mouse gene, which is a paralog of mouse gene Oasl1, the ortholog of this gene

Further reading

• Mackay V, Linn S . Selective inhibition of the dnase activity of the recBC enzyme by the DNA binding protein from Escherichia coli. . J. Biol. Chem. . 251 . 12 . 3716–9 . 1976 . 10.1016/S0021-9258(17)33402-6 . 776974 . free .
• Lee JW, Choi HS, Gyuris J, etal . Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor. . Mol. Endocrinol. . 9 . 2 . 243–54 . 1995 . 10.1210/mend.9.2.7776974 . 7776974 . free .
• Hartmann R, Olsen HS, Widder S, etal . p59OASL, a 2'-5' oligoadenylate synthetase like protein: a novel human gene related to the 2'-5' oligoadenylate synthetase family . Nucleic Acids Res. . 26 . 18 . 4121–8 . 1998 . 9722630 . 10.1093/nar/26.18.4121 . 147837 .
• Rebouillat D, Marié I, Hovanessian AG . Molecular cloning and characterization of two related and interferon-induced 56-kDa and 30-kDa proteins highly similar to 2'-5' oligoadenylate synthetase . Eur. J. Biochem. . 257 . 2 . 319–30 . 1998 . 9826176 . 10.1046/j.1432-1327.1998.2570319.x . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Andersen JB, Strandbygård DJ, Hartmann R, Justesen J . Interaction between the 2'-5' oligoadenylate synthetase-like protein p59 OASL and the transcriptional repressor methyl CpG-binding protein 1 . Eur. J. Biochem. . 271 . 3 . 628–36 . 2004 . 14728690 . 10.1046/j.1432-1033.2003.03966.x . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Scherer SE, Muzny DM, Buhay CJ, etal . The finished DNA sequence of human chromosome 12 . Nature . 440 . 7082 . 346–51 . 2006 . 16541075 . 10.1038/nature04569 . 2006Natur.440..346S . free .

Notes and References

1. Hovnanian A, Rebouillat D, Levy ER, Mattei MG, Hovanessian AG . The human 2',5'-oligoadenylate synthetase-like gene (OASL) encoding the interferon-induced 56-kDa protein maps to chromosome 12q24.2 in the proximity of the 2',5'-OAS locus . Genomics . 56 . 3 . 362–3 . May 1999 . 10087211 . 10.1006/geno.1998.5737 .
2. Web site: Entrez Gene: OASL 2'-5'-oligoadenylate synthetase-like.
3. Kell AM, Gale M . RIG-I in RNA virus recognition . Virology . 479-480 . 110–121 . May 2015 . 25749629 . 4424084 . 10.1016/j.virol.2015.02.017 .
4. Zhu J, Zhang Y, Ghosh A, Cuevas RA, Forero A, Dhar J . etal. Antiviral activity of human OASL protein is mediated by enhancing signaling of the RIG-I RNA sensor. . Immunity . 2014 . 40 . 6 . 936–48 . 24931123 . 10.1016/j.immuni.2014.05.007 . 4101812 .
5. Choi . Un Yung . Kang . Ji-Seon . Hwang . Yune Sahng . Kim . Young-Joon . Oligoadenylate synthase-like (OASL) proteins: dual functions and associations with diseases . Experimental & Molecular Medicine . 47 . 3 . 2015-03-06 . 2092-6413 . 25744296 . 4351405 . 10.1038/emm.2014.110 . e144.
6. Rex . Viktoria . Stempel . Markus . Halle . Stephan . Brinkmann . Melanie M . The two faces of oligoadenylate synthetase-like: effective antiviral protein and negative regulator of innate immunity . Current Opinion in Virology . 60 . 2023 . 10.1016/j.coviro.2023.101329 . 101329. 37079941 .
7. Leisching G, Wiid I, Baker B. The Association of OASL and Type I Interferons in the Pathogenesis and Survival of Intracellular Replicating Bacterial Species. . Front Cell Infect Microbiol . 2017 . 7 . 196 . 28580319 . 10.3389/fcimb.2017.00196 . free . 5437694 .
8. de Toledo-Pinto TG, Ferreira AB, Ribeiro-Alves M, Rodrigues LS, Batista-Silva LR, Silva BJ . etal. STING-Dependent 2'-5' Oligoadenylate Synthetase-Like Production Is Required for Intracellular Mycobacterium leprae Survival. . J Infect Dis . 2016 . 214 . 2 . 311–20 . 27190175 . 10.1093/infdis/jiw144 .