The expression of both domains of the 69/71 kDa 2',5' oligoadenylate synthetase generates a catalytically active enzyme and mediates an anti-viral response.
The 2',5' oligoadenylate synthetase (OAS) represents a family of interferon-induced proteins which, when activated by double-stranded (ds) RNA, polymerizes ATP into 2',5'-linked oligomers with the general formula pppA(2'p5'A)n, where n >/= 1. The 69-kDa form of human OAS has two isoforms (p69 and p71) that are identical for their first 683 amino acids and consist of two homologous and adjacent domains, each homologous to the small 40-kDa OAS. Here, we demonstrate that mRNA species specific for the isoforms p69 and p71 are enhanced in interferon-treated cells, with the p69 mRNA being more abundant than that of p71. In transfected cells, both isoforms could be expressed independently to generate enzymes with similar catalytic activity, typical of the natural 69-kDa OAS from interferon-treated cells. On the other hand, deletion mutants expressing either the N- or C-terminal domain common in p69 and p71 were greatly unstable and were found to be devoid of catalytic activity, in spite of the capacity of the C-terminal domain to bind dsRNA. Finally, we show that murine cell lines stably expressing either p69 or p71 isoforms partially resist infection by the encephalomyocarditis virus. These results indicate that both isoforms of the 69-kDa form of 2',5' OAS are expressed in interferon-treated cells, and that each isoform could be implicated in the mechanism of the anti-viral action of interferon.
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Unité de Virologie et Immunologie Cellulaire, UA CNRS 1930, Institut Pasteur, Paris, France.
Rebouillat
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Hovanessian
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D015088:2',5'-Oligoadenylate Synthetase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D002460:Cell Line; D002999:Clone Cells; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
D000998:Antiviral Agents; D020033:Protein Isoforms; D012333:RNA, Messenger; D015088:2',5'-Oligoadenylate Synthetase