The interferon-induced enzyme 2–5A synthetase adenylates tRNA

Justesen, Just; Worm-Leonhard, H.; Ferbus, Didier; Petersen, Hans Uffe

doi:10.1016/s0300-9084(85)80207-8

Cited by 10 publications

(4 citation statements)

References 10 publications

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“…a preformed 2-5A molecule or to a nucleotide with the structure RpA like NAD ϩ , A p4 A, and tRNA (35)(36)(37)(38). However, biological relevance of these latter modified nucleotides is not yet clear.…”

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confidence: 99%

The 100-kDa 2′,5′-Oligoadenylate Synthetase Catalyzing Preferentially the Synthesis of Dimeric pppA2′p5′A Molecules Is Composed of Three Homologous Domains

Rebouillat

Hovnanian

Marié

et al. 1999

Journal of Biological Chemistry

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The 2-5A synthetases represent a family of proteins implicated in the mechanism of the antiviral action of interferon. When activated by double-stranded RNA, these proteins polymerize ATP into 2-5-linked oligomers with the general formula pppA(2p5A) n , n > 1. Three forms of human 2-5A synthetases have been described corresponding to proteins of 40/46 (p40/p46), 69/71 (p69/p71), and 100 kDa (p100). Here we describe the molecular cloning and characterization of p100. By screening a cDNA expression library with a specific p100 polyclonal antibody, we first isolated a 590-nucleotide cDNA fragment which was subsequently used to isolate the full-length 6365-nucleotide cDNA. This cDNA recognizes a distinct interferon-induced messenger RNA of 7 kilobases. It has an open reading frame encoding a protein of 1087 amino acids including the sequence of seven peptides obtained by microsequencing of the natural p100 protein, which was purified from interferon-treated human cells. p100 is composed of three adjacent domains, each homologous to the previously defined catalytic unit of 350 amino acids, which is present as one unit in p40/p46 and as two units in p69/p71. The recombinant p100 synthesized preferentially dimeric 2,5-oligoadenylate molecules and displayed parameters for maximum enzyme activity similar to the natural p100. These results confirm that the enzymatic activity of p100 is distinct compared with that of p40/p46 and p69/p71.

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confidence: 99%

The 100-kDa 2′,5′-Oligoadenylate Synthetase Catalyzing Preferentially the Synthesis of Dimeric pppA2′p5′A Molecules Is Composed of Three Homologous Domains

Rebouillat

Hovnanian

Marié

et al. 1999

Journal of Biological Chemistry

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“…In addition to the synthesis of 2-5A molecules, partially purified (2'-5')oligoadenylate synthetase preparations have been shown to catalyze in vitro the transfer of a nucleotide monophosphate moiety to the 2'-OH end of a preformed 2-5A molecule or to a nucleotide with the structure RpA like NAD', adenosine-(S')tetraphospho(2')adenosine (A,,A) and tRNA (Ball and White, 1979;Justesen et al, 1980;Cayley and Kerr, 1982;Justesen et al, 1985). However, biological relevance of these latter modified nucleotides is not yet clear.…”

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confidence: 99%

69‐kDa and 100‐kDa Isoforms of Interferon‐Induced (2′‐5′)Oligoadenylate Synthetase Exhibit Differential Catalytic Parameters

Marié

Blanco

Rebouillat

et al. 1997

European Journal of Biochemistry

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The (2'-S')oligoadenylate synthetase represents a family of interferon-induced proteins which when activated by double-stranded (ds)RNA polymerizes ATP into 2'-S'-linked oligomers with the general formula pppA(2'pS'A),, where n > 1, which for convenience are referred to as 2-5A. We studied here the influence of pH, dsRNA concentration and time on oligomeric composition of 2-5A synthesized by purified 69-kDa and 100-kDa isoforms of (2'-S')oligo(adenylate) synthetase. In optimal conditions for activity, the 69-kDa forin synthesized higher oligomers of 2-5A molecules whereas the 100 kDa form synthesized preferentially dinieric molecules, which are known not to be functional for the activation of RNase L. This difference does not reflect a differential affinity of the enzymes for the preformed 2-SA dimer, which is found to be a very poor substrate for both enzymes. This latter strongly suggests that the mechanism of elongation is more likely processive. Moreover, we show that both isoforms have efficient nucleotidyl-transferase activity and provide evidence that, in optimized conditions, GTP can be used alone as substrate by these enzymes to generate pppG2'pS'G. Our results clearly demonstrate that the 69-kDa and 100-kDa forms of (2'-5')oligoadenylate synthetase manifest various differential catalytic activities, and favor the hypothesis that these enzymes might have other functions in the cell besides those in the 2-5A system.

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“…Furthermore, the p40/p46 and p69/p71 could be differentiated from p100 by their specific subcellular localization and enzymatic parameters, thus suggesting that they might have distinct functions (Chebath et al, 1987a;Hovanessian et al, 1987Hovanessian et al, , 1988Marié et al, 1990a;Witt et al, 1993). In addition to the synthesis of 2-5A molecules, partially purified OAS preparations have been shown to catalyze in vitro the transfer of a nucleotide monophosphate moiety to the 2Ј-OH end of a nucleotide with the structure RpA, like NAD ϩ , A p4 A, and tRNA (Ball and White, 1979;Cayley and Kerr, 1982;Justesen et al, 1980Justesen et al, , 1985Marié et al, 1997). However, biological relevance of these latter modified nucleotides is not yet clear.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1998

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The interferon-induced enzyme 2–5A synthetase adenylates tRNA

Cited by 10 publications

References 10 publications

The 100-kDa 2′,5′-Oligoadenylate Synthetase Catalyzing Preferentially the Synthesis of Dimeric pppA2′p5′A Molecules Is Composed of Three Homologous Domains

The 100-kDa 2′,5′-Oligoadenylate Synthetase Catalyzing Preferentially the Synthesis of Dimeric pppA2′p5′A Molecules Is Composed of Three Homologous Domains

69‐kDa and 100‐kDa Isoforms of Interferon‐Induced (2′‐5′)Oligoadenylate Synthetase Exhibit Differential Catalytic Parameters

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

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