Propagation of stochastic fluctuations in RNA polymerase abundance in constitutive gene expression

Abstract

Varied abundance of gene expression machineries, such as RNA polymerase (RNAP) or ribosome, comprises a source of cell-to-cell variability in gene expression. Thus introduced extrinsic “noise” at the transcriptional or translational stage of gene expression may well propagate to the downstream pathways, bringing about phenotypic variability. To explore the possibilities and conditions for these fluctuations to average out or sustain, or even amplify along the information processing pathway of central dogma, we studied the stochastic model of gene expression, where the varying RNAP copy number acts as a major source of extrinsic noise. We find that the noise in the downstream protein expression can be mitigated when varied RNAP availability is incorporated with less efficient but steady translation, which is the case of the bacteriophage T7 RNAP-based expression system often employed in synthetic biology applications.