Effects of extrinsic noise are promoter kinetics dependent

Studies in Escherichia coli using in vivo single-RNA detection and time-lapse confocal microscopy showed that transcription is a multiple rate-limiting steps process, in agreement with previous in vitro measurements. Here, from simulations of a stochastic model of transcription validated empirically that accounts for cell-to-cell variability in RNA polymerase (RNAP) numbers, we investigate the hypothesis that the cell-to-cell variability in RNA numbers due to RNAP variability differs with the promoter rate-limiting steps dynamics. We find that increasing the cell-to-cell variability in RNAP numbers increases the cell-to-cell diversity in RNA numbers, but the degree with which it increases is promoter kinetics dependent. Namely, promoters whose open complex formation is relatively longer lasting dampen more efficiently this noise propagation phenomenon. We conclude that cell-to-cell variability in RNA numbers due to variability in RNAP numbers is promoter-sequence dependent and, thus, evolvable.Peer reviewe