Disease relevance of relA

• Reversal of growth retardation by L-isoleucine, accumulation of guanosine 5'-diphosphate 3'-diphosphate (magic spot), and relA mutant hypersensitivity suggest sulfometuron methyl interference with branched-chain amino acid biosynthesis [1].
• Identification and characterization of a relA-dependent starvation-inducible locus (sin) in Salmonella typhimurium [2].
• To determine the effect of ppGpp, a stringent (relA+) and relaxed (relA) isogenic pair of E. coli K-12 strains was starved for isoleucine, and the residual rate of synthesis of this enzyme was measured [3].

High impact information on relA

• In vivo derepression of the his operon is markedly defective when histidine starvation is imposed on a relA mutant--unable to rapidly increase synthesis of ppGpp--growing in amino-acid-rich medium [4].
• Since not all relA-dependent sti loci are induced during both C- and N-starvation, we propose that two separate ppGpp-dependent pathways function during C-starvation and N-starvation, respectively [5].
• In addition, derepression of his expression by novobiocin and its repression by anaerobiosis or osmolarity are independent of the stringent response gene, relA [6].
• In addition, all four loci are under positive regulation by the relA gene product (i.e., ppGpp) during C- or N-starvation, but not P-starvation [5].
• This role was independent of the relA gene (previously found to be needed for stiB induction) [7].

Associations of relA with chemical compounds

• Mutants lacking 4-thiouridine (nuv) and mutants defective in the synthesis of ppGpp (guanosine 5'-diphosphate-3'-diphosphate) (relA) were found to be sensitive to killing by near-UV [8].
• The introduction of relA into the sinA-lac strain prevented induction by nicotinate starvation and partially prevented induction by phosphate starvation [2].
• The relA mutant again failed to resume growth after a shift from glucose-ammonia to glucose-arginine medium [9].

Other interactions of relA

• One carbon-starvation-inducible lac fusion, designated stiA was previously reported to be a sigma(S)-dependent SSR locus that is phosphate-starvation, nitrogen-starvation and H2O2 inducible, positively regulated by (p)ppGpp in a relA-dependent manner, and negatively regulated by cAMP:cAMP receptor protein complex and OxyR [10].
• In this study, we found that relA and spoT double mutant Salmonella (DeltappGpp strain), which is defective in ppGpp synthesis, was virtually avirulent in BALB/c mice [11].

References