title: Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA.
abstract: Prokaryotic chromosomes encode toxin-antitoxin loci, often in multiple copies. In most cases, the function of these genes is not known. The chpA (mazEF) locus of Escherichia coli has been described as a cell killing module that induces bacterial apoptosis during nutritional stress. However, we found recently that ChpAK (MazF) does not confer cell killing but rather, induces a bacteriostatic condition from which the cells could be resuscitated. Results presented here yield a mechanistic explanation for the detrimental effect on cell growth exerted by ChpAK and the homologous ChpBK protein of E.coli. We show that both proteins inhibit translation by inducing cleavage of translated mRNAs. Consistently, the inhibitory effect of the proteins was counteracted by tmRNA. Amino acid starvation induced strong transcription of chpA that depended on Lon protease but not on ppGpp. Simultaneously, ChpAK cleaved tmRNA in its coding region. Thus, ChpAK and ChpBK inhibit translation by a mechanism very similar to that of E.coli RelE. On the basis of these results, we propose a model that integrates TA loci into general prokaryotic stress physiology.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Christensen
authors.forename: Kim
authors.initials: K
authors.lastname: Pedersen
authors.forename: Flemming G
authors.initials: FG
authors.lastname: Hansen
authors.forename: Kenn
authors.initials: K
authors.lastname: Gerdes
mesh_terms: D049069:ATP-Dependent Proteases; D000596:Amino Acids / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002876:Chromosomes, Bacterial; D003062:Codon; D004926:Escherichia coli / Q000502:physiology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D049070:Protease La; D014176:Protein Biosynthesis; D012329:RNA, Bacterial / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000596:Amino Acids; D001427:Bacterial Toxins; C465568:ChpAK protein, E coli; D003062:Codon; D029968:Escherichia coli Proteins; D006150:Guanine Nucleotides; D006360:Heat-Shock Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; C096222:tmRNA; D049069:ATP-Dependent Proteases; D012697:Serine Endopeptidases; C483567:Lon protein, E coli; D049070:Protease La