Comments on the Role of Aminoacyl-tRNA in the Regulation of Amino Acid Biosynthesis

Abstract

The report by Eidlic and Neidhardt (1965) that reduced charging of acceptor tRNA^Val in Escherichia coli was accompanied by derepression of the isoleucine and valine biosynthetic enzymes is as important to bacterial physiology as the earlier finding by Cohen and Jacob (1959) of mutations (trpR) unlinked to the trp gene cluster that lead to derepression of a tryptophan biosynthetic enzyme. The discovery of trpR, along with analogous mutations affecting arginine biosynthesis (Gorini et al. 1962; Maas 1962), was certainly instrumental in justifying Jacob and Monod’s extension (1962) of the operator-repressor model of gene control to biosynthetic systems. Although the Eidlic-Neidhart observation was not immediately followed by the formulation of an equally useful model, it was followed by a flurry of activity, primarily with bacteria, in many laboratories reporting the existence or nonexistence of a similar effect of limited charging of other tRNAs on the respective pathways.

Neidhardt and his coworkers were not guilty of the most common interpretation—that when an inverse correlation was found between the level of charging by a given amino acid and the amount of biosynthetic enzyme activity, it was not the free amino acid that bound to the repressor but an aminoacyl-tRNA. Some workers suggested that certain aminoacyl-tRNAs had distinct regulatory roles but, at most, only minor roles in protein synthesis. A more operational interpretation was that the aminoacyl-tRNA synthetase was involved in the level of expression of the cognate amino acid biosynthetic pathway and that the data did not allow the decision between the...