Growth-rate-dependent partitioning of RNA polymerases in bacteria.
Physiological changes that result in changes in bacterial gene expression are often accompanied by changes in the growth rate for fast adapting enteric bacteria. Because the availability of RNA polymerase (RNAP) in cells depends on the growth rate, transcriptional control involves not only the regulation of promoters, but also depends on the available (or free) RNAP concentration, which is difficult to quantify directly. Here, we develop a simple physical model describing the partitioning of cellular RNAP into different classes: RNAPs transcribing mRNA and ribosomal RNA (rRNA), RNAPs nonspecifically bound to DNA, free RNAP, and immature RNAP. Available experimental data for Escherichia coli allow us to determine the 2 unknown parameters of the model and hence deduce the free RNAP concentration at different growth rates. The results allow us to predict the growth-rate dependence of the activities of constitutive (unregulated) promoters, and to disentangle the growth-rate-dependent regulation of promoters (e.g., the promoters of rRNA operons) from changes in transcription due to changes in the free RNAP concentration at different growth rates. Our model can quantitatively account for the observed changes in gene expression patterns in mutant E. coli strains with altered levels of RNAP expression without invoking additional parameters. Applying our model to the case of the stringent response after amino acid starvation, we can evaluate the plausibility of various scenarios of passive transcriptional control proposed to account for the observed changes in the expression of rRNA and biosynthetic operons.
Klumpp
Stefan
S
Center for Theoretical Biological Physics and Department of Physics, University of California at San Diego, La Jolla, CA 92093-0374, USA. klumpp@ctbp.ucsd.edu
Hwa
Terence
T
D001419:Bacteria / Q000201:enzymology* / Q000254:growth & development; D012321:DNA-Directed RNA Polymerases / Q000502:physiology*; D029968:Escherichia coli Proteins; D005786:Gene Expression Regulation; D009876:Operon; D011401:Promoter Regions, Genetic; D012335:RNA, Ribosomal
D029968:Escherichia coli Proteins; D012335:RNA, Ribosomal; D012321:DNA-Directed RNA Polymerases