ABSTRACT
Transcription bursting creates variation among the individuals of a given population. Bursting emerges as the consequence of repeated turning on and off the transcription process. There are at least three sub-processes involved in the mechanism of transcription bursting with different timescale regimes viz. flipping dynamics across the on-off states, microscopic transcription elongation events and the mesoscopic transcription dynamics along with the mRNA recycling. We demonstrate that when the flipping dynamics is coupled with the microscopic elongation events, then the distribution of the resultant transcription rates will be over-dispersed. This in turn reflects as the transcription bursting with over-dispersed non-Poisson type distribution of mRNA numbers. We further show that there exist optimum flipping rates (αC, βC) at which the stationary state Fano factor and variance associated with the mRNA numbers attain maxima. Here α is the rate of flipping from the on-state to the off-state, β is the rate of flipping from the off-state to the on-state. When α = β = χ with zero rate in the off-state channel, then there exist optimum flipping rates at which the non-stationary Fano factor and variance attain maxima. Close observation of the transcription mechanism reveals that the RNA polymerase performs several rounds of stall-continue type dynamics before generating a complete mRNA. Based on this observation, we model the transcription event as a stochastic trajectory of the transcription machinery across these on-off state elongation channels. Each mRNA transcript follows different trajectory. The total time taken by a given trajectory is the first passage time (FPT). Inverse of this FPT is the resultant transcription rate associated with the particular mRNA. Therefore, the time required to generate a given mRNA transcript will be a random variable.
- Transcription bursting
- on-off state flipping
- over-dispersion
- Fano factor
- mRNA dynamics
- non-Poisson distribution
Footnotes
↵* Email: rmurugan{at}gmail.com. Phone: +91 44 2257 4116.
author ORCID link was corrected;