Role of mRNA gestation and senescence in noise reduction during the cell cycle.

ABSTRACT

Recent innovations in experimental techniques on single molecule detection resulted in advances in the quantification of molecular noise in several systems, and provide suitable data for defining stochastic computational models of biological processes. Some of the latest stochastic models of cell cycle regulation analyzed the effect of noise on cell cycle variability. In their study, Kar et al. (Proc. Natl. Acad. Sci. USA 106, 6471-6476, 2009) found that the observed variances of cell cycle time and cell division size distributions cannot be matched with the measured long half-lives of mRNAs. Here, we investigate through modeling and simulation how the noise created by the transcription and degradation processes of a key cell cycle controller mRNA affect the statistics of cell cycle time and cell size at division. Our model consists of an encoding of the model of Kar et al. into a stochastic Petri net, with the extensions necessary to represent multiple synthesis (gestation) and degradation (senescence) steps in the regulation of mRNAs. We found that few steps of gestation and senescence of mRNA are enough to give a good match for both the measured half-lives and variability of cell cycle-statistics. This result suggests that the complex process of transcription can be more accurately approximated by multi-step linear processes.