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. 133:830-843, 1978) that the level of the enzyme in Salmonella typhimurium LT-2 strain SB3436 is invariant. The basis for the difference in the growth-rate-dependent regulation between the two genera was investigated. Expression of gnd, which encodes 6-phosphogluconate dehydrogenase, was growth rate uninducible in strain SB3436, as reported previously, but it was 1.4-fold growth rate inducible in other S. typhimurium LT-2 strains, e.g., SA535. Both the SB3436 and SA535 gnd genes were growth rate inducible in E. coli K-12. Moreover, the nucleotide sequences of the regulatory regions of the two S. typhimurium genes were identical. We concluded that a mutation unlinked to gnd is responsible for the altered growth rate inducibility of 6-phosphogluconate dehydrogenase in strain SB3436. Transductional analysis showed that the altered regulation is due to the presence of a mutation in hisT, the gene for the tRNA modification enzyme pseudouridine synthetase I. A complementation test showed that the regulatory defect conferred by the hisT mutation was recessive. In E. coli, hisT mutations reduced the extent of growth rate induction by the same factor as in S. typhimurium. The altered regulation conferred by hisT mutations was not simply due to their general effect of reducing the polypeptide chain elongation rate, because miaA mutants, which lack another tRNA modification and have a similarly reduced chain growth rate, had higher rather than lower 6-phosphogluconate dehydrogenase levels. Studies with genetic fusions suggested that hisT mutations lower the gnd mRNA level. The data also indicated that hisT is involved in translational control of gnd expression, but not the aspect mediated by the internal complementary sequence.Growth-rate-dependent regulation alters the synthesis rate and/or the relative amount of a given protein in response to changes in growth rate (39; reviewed in reference 53). The accumulation rate of some proteins is proportional to growth rate, such that the amount of the protein relative to total protein is constant. For other proteins, the accumulation rate increases in proportion to the square of the growth rate, and thus the relative amount of these proteins increases in proportion to the growth rate. The accumulation rate for a third class of proteins is constant, with the result that the level of these proteins is inversely proportional to the growth rate. The mechanism for this regulation is not yet completely understood for any gene (for reviews, see references 17, 24, and 26).The gnd genes of Escherichia coli K-12 and Salmonella typhimurium LT-2 are among the few nonribosomal genes whose growth-rate-dependent regulation is currently under investigation. The genes (6), the accumulation rate of gnd mRNA varies in proportion to growth rate, and so does translational efficiency. In other words, growth-rate-dependent regulation of 6PGD expression in E. coli K-12 is subject to translational control as well as to control of either gnd transcription or mRNA stability. Regulation of translationa...

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