Stochasticity in gene expression affects many cellular processes and is a source of phenotypic diversity between genetically identical individuals. Events in elongation, particularly RNA polymerase pausing, are a source of this noise. Since the rate and duration of pausing are sequence-dependent, this regulatory mechanism of transcriptional dynamics is evolvable. The dependency of pause propensity on regulatory molecules makes pausing a response mechanism to external stress. Using a delayed stochastic model of bacterial transcription at the single nucleotide level that includes the promoter open complex formation, pausing, arrest, misincorporation and editing, pyrophosphorolysis, and premature termination, we investigate how RNA polymerase pausing affects a gene's transcriptional dynamics and gene networks. We show that pauses' duration and rate of occurrence affect the bursting in RNA production, transcriptional and translational noise, and the transient to reach mean RNA and protein levels. In a genetic repressilator, increasing the pausing rate and the duration of pausing events increases the period length but does not affect the robustness of the periodicity. We conclude that RNA polymerase pausing might be an important evolvable feature of genetic networks.
Investigation on how phenotypic diversity of genetically identical organisms is generated and regulated has focused on noise in gene expression. It is unknown to what extent noise in gene expression and genetic networks is evolvable, and by which mechanisms it evolves. The noise has several sources, e.g., noise in transcription initiation and during elongation. We focus on RNA polymerase (RNAP) pausing and show that it can regulate, to some extent, noise in gene expression. RNAP frequently pauses during elongation. The pausing frequency and average duration are sequence-specific, thus evolvable. The dependency of pause propensity on regulatory molecules makes pausing a mechanism adaptable to rapidly changing environments. We study, in a stochastic model of bacterial transcription at the single nucleotide level that includes the promoter open complex formation, pausing, arrest, misincorporation and editing, pyrophosphorolysis, and premature termination, how pausing affects the dynamics of gene expression and gene networks. In a model of a genetic clock, with periodic dynamics, pauses affect the period length but do not disrupt the periodicity. We conclude that RNAP pausing is an important evolvable feature of gene regulatory networks, that can be used by organisms to adapt to changing environments and regulate phenotypic diversity.