AppppA and related adenylylated nucleotides are synthesized as a consequence of oxidation stress

doi:10.1016/0092-8674(84)90318-0

Cell

Volume 37, Issue 1, May 1984, Pages 225-232

https://doi.org/10.1016/0092-8674(84)90318-0 Get rights and content

Abstract

AppppA, ApppGpp, AppppG, ApppG, and ApppA rapidly accumulate to high levels in Salmonella typhimurium following exposure to a variety of oxidizing agents, but not to a variety of other stresses. Among the agents inducing these adenylylated nucleotides are 1-chloro-2,4-dinitrobenzene, diamide, hydrogen peroxide, t-butyl hydroperoxide, N-ethyl maleimide, iodoacetamide, cadmium chloride, and a variety of quinones. Some of these oxidizing agents cause preferential synthesis of specific adenylylated nucleotides, e.g., N-ethyl maleimide induces ApppA and menadione induces ApppGpp. Our data, as well as other evidence in the literature, strongly suggest that oxidation stress is coupled to adenylylated nucleotide synthesis by aminoacyl-tRNA synthetases. Although adenylylated nucleotides are made by tRNA synthetases in vitro, their synthesis in vivo is not a simple consequence of inhibition of synthetase activity. Compounds that inhibit normal charging by aminoacyl-tRNA synthetases do not result in the synthesis of adenylylated nucleotides, nor do mutations in tRNA synthetase structural genes or tRNA structural, modifying, or processing genes. We propose that the family of adenylylated nucleotides are alarmones signaling the onset of oxidation stress, and that particular ones may be alarmones for specific oxidative stresses, e.g., ApppGpp for oxidative damage to amino acid biosynthesis.

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^∗: Present address: Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California 94080.

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Cell

ArticleAppppA and related adenylylated nucleotides are synthesized as a consequence of oxidation stress

Abstract

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Mutants of Salmonella typhimurium with an altered leucyl-transfer ribonucleic acid synthetase

J. Bacteriol.

Transport of antibiotics and metabolite analogs by systems under cyclic AMP control: positive selection of Salmonella typhimurium cya and crp mutants

J. Bacteriol.

The leader mRNA of the histidine attenuator region resembles tRNAHis: possible general regulatory implications

Phenylalanyl transfer ribonucleic acid synthetase from Escherichia coli B. Potent inhibition by analogues of N-benzyl-2-phenylethylamine

J. Med. Chem.

The role of zinc in 5′,5′-diadenosine tetraphosphate production by aminoacyl-transfer RNA synthetases

Mol. Cell. Biochem.

Biosynthesis of tRNA in histidine regulatory mutants of Salmonella typhimurium

Nucl. Acids Res.

Regulation of bacterial ppGpp and pppGpp

Ann. Rev. Microbiol.

Sulfhydryl groups in aminoacyl-tRNA synthetases

Mutagenicity of quinones: pathways of metabolic activation and detoxification

Inducible repair of oxidative DNA damage in E. coli

Nature

Sulphur metabolism: the usefulness of N-ethylmaleimide

Nature

Occurrence of glutathione in bacteria

J. Bacteriol.

Mapping of the locus for Escherichia coli transfer ribonucleic acid nucleotidyltransferase

J. Bacteriol.

Article
AppppA and related adenylylated nucleotides are synthesized as a consequence of oxidation stress

The leader mRNA of the histidine attenuator region resembles tRNA^His: possible general regulatory implications