Overall controls on the biosynthesis of ribosomes in growing bacteria

Abstract

Under conditions of balanced growth, there is a relationship between λ, the growth rate constant and k r , the rate of synthesis of ribosomal RNA per unit amount of DNA. If k is the rate of protein synthesis per unit of ribosomal RNA and C is the ratio of DNA to protein; this relationship is k r = λ 2/ kC. It applies if proteins and ribosomes are stable and ribosomal precursors are present in small amounts. From direct estimates of k r from isotope incorporation rates, or indirectly from the relationship k r = ( r) λ/( d), it could be shown that as the growth rate is changed by a given factor through alteration of the nutritional environment, k r is altered by an even larger factor. These findings imply strong physiological control at the level of RNA synthesis. However, the change is not sufficiently large to make k r directly proportional to λ 2, which would be the case if C and k are constant, independent of the growth rate. Since C is, in experimental fact, essentially independent of growth rate, this is another way of saying that the rate of net protein synthesis per unit amount of ribosomal RNA is not constant. Although this would appear to cast doubt on the hypothesis of Maaløe and Kjeldgaard that protein synthesis by the ribosome has the same efficiency for balanced growth at any rate, there are several other alternative explanations for the “extra RNA” in slowly growing cells. Experimental studies from our laboratory to examine these possibilities are reviewed. Protein turnover, ribosome turnover, destruction of precursors to ribosomes can be excluded as the major raison d'être of the “extra” RNA for slowly growing chemostat cultures limited by the carbon source. Also, the presence of cells temporarily quiescent in protein synthesis cannot account quantitatively for this RNA. The “extra” RNA cannot be accounted for by assuming that the addition of an amino acid to a growing peptide chain takes longer in cells in a poor environment and therefore the synthesis of protein by a functioning ribosome is slower. However, experiments based on the theory presented here show that the “extra” RNA in the carbon-limited slow-growing cells is available in the cells in a form that can quickly function when the environment is enriched. It must be in the form of ribosomes and tRNA ready, or almost ready, to function, but not functioning at full efficiency in the poor environment.