ppGpp Formation in Escherichia coli Treated with Rifampicin

It has been previously reported that the accumulation of the regulatory nucleotide ppGpp (MS I), which is governed by the RC gene of Escherichia coli, does not occur in the presence of rifampicin. Since this drug inhibits RNA chain initiation, it was suggested that the formation of ppGpp is somehow dependent on the presence of nascent RNA chains (Wong, J. T.-F., and Nazar, R. N., J. Biol. Chem., 245, 4591 (1970)). We find that this effect of rifampicin depends on amino acid activation: when valyl-tRNA synthetase is specifically inactivated, then ppGpp accumulation proceeds in rifampicin despite complete inhibition of RNA synthesis. The effect of rifampicin on ppGpp formation is therefore indirect, and probably reflects the recharging of transfer RNA due to the fact that the rate of protein synthesis drops in rifampicin-treated cells.