Delayed‐relaxed response explained by hyperactivation of RelE

Summary Escherichia coli encodes two rel loci, both of which contribute to the control of synthesis of macromolecules during amino acid starvation. The product of relA (ppGpp synthetase I) is responsible for the synthesis of guanosine tetraphosphate, ppGpp, the signal molecule that exerts stringent control of stable RNA synthesis. The second rel locus, relBE, was identified by mutations in relB that confer a so‐called ‘delayed‐relaxed response’ characterized by continued RNA synthesis after a lag period of ≈ 10 min after the onset of amino acid starvation. We show here that the delayed‐relaxed response is a consequence of hyperactivation of RelE. As in wild‐type cells, [ppGpp] increased sharply in relB101 relE cells after the onset of starvation, but returned rapidly to the prestarvation level. RelE is a global inhibitor of translation that is neutralized by RelB by direct protein–protein interaction. Lon protease activates RelE during amino acid starvation by degradation of RelB. We found that mutations in relB that conferred the delayed‐relaxed phenotype destabilized RelB. Such mutations confer severe RelE‐dependent inhibition of translation during amino acid starvation, indicati