The human 2'-5'oligoadenylate synthetase family: unique interferon-inducible enzymes catalyzing 2'-5' instead of 3'-5' phosphodiester bond formation.
The demonstration by Kerr and colleagues that double-stranded (ds) RNA inhibits drastically protein synthesis in cell-free systems prepared from interferon-treated cells, suggested the existence of an interferon-induced enzyme, which is dependent on dsRNA. Consequently, two distinct dsRNA-dependent enzymes were discovered: a serine/threonine protein kinase that nowadays is referred to as PKR and a 2'-5'oligoadenylate synthetase (2'-5'OAS) that polymerizes ATP to 2'-5'-linked oligomers of adenosine with the general formula pppA(2'p5'A)(n), n>or=1. The product is pppG2'p5'G when GTP is used as a substrate. Three distinct forms of 2'-5'OAS exist in human cells, small, medium, and large, which contain one, two, and three OAS units, respectively, and are encoded by distinct genes clustered on the 2'-5'OAS locus on human chromosome 12. OASL is an OAS like IFN-induced protein encoded by a gene located about 8 Mb telomeric from the 2'-5'OAS locus. OASL is composed of one OAS unit fused at its C-terminus with two ubiquitin-like repeats. The human OASL is devoid of the typical 2'-5'OAS catalytic activity. In addition to these structural differences between the various OAS proteins, the three forms of 2'-5'OAS are characterized by different subcellular locations and enzymatic parameters. These findings illustrate the apparent structural and functional complexity of the human 2'-5'OAS family, and suggest that these proteins may have distinct roles in the cell.
Hovanessian
Ara G
AG
UPR 2228 CNRS, UFR Biomédicale, Université René Descartes, 45 rue des Saints Pères, 75270 Paris Cedex 06, France. ara.hovanessian@univ-paris5.fr
Justesen
Just
J
D015088:2',5'-Oligoadenylate Synthetase / Q000737:chemistry* / Q000502:physiology*; D000818:Animals; D002384:Catalysis; D020134:Catalytic Domain; D002881:Chromosomes, Human, Pair 12 / Q000737:chemistry; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000737:chemistry; D007372:Interferons / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D008957:Models, Genetic; D005810:Multigene Family; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000737:chemistry; D011994:Recombinant Proteins; D025801:Ubiquitin / Q000737:chemistry
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D011994:Recombinant Proteins; D025801:Ubiquitin; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase