Prokaryotic toxin–antitoxin stress response loci

Abstract

Prokaryotic toxin–antitoxin (TA) loci, such as relBE and mazEF, encode mRNA-cleaving enzymes that are activated by nutritional stress. Slowly growing bacteria and Archaea have numerous TA loci. For example, Mycobacterium tuberculosis has 38 and Sulfolobus tokodaii has 32 TA loci. Free-living bacteria have many TA loci whereas obligate intracellular organisms have none, consistent with a hypothesis that TA loci function as part of the cellular stress response. RelE cleaves mRNA codons positioned at the ribosomal A-site, between the 2nd and 3rd nucleotide. RelE does not cleave naked mRNA in vitro if ribosomes aren't present. Whereas mRNA cleavage by RelE is strictly dependent on the presence of ribosomes, MazF cleaves mRNAs site-specifically at ACA sites independently of the ribosomes. Whether the ribosomes have a role in MazF-mediated mRNA cleavage during physiological conditions is not resolved. TA loci function as stress response elements that help the cells cope with nutritional stress, possibly by reducing the production of defective proteins during scarce conditions.