Probing Mechanisms of Transcription Elongation Through Cell-to-Cell Variability of RNA Polymerase
Program in Systems Biology; Department of Microbiology and Physiological Systems
Biochemical Phenomena, Metabolism, and Nutrition | Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Enzymes and Coenzymes | Systems Biology
The process of transcription initiation and elongation are primary points of control in the regulation of gene expression. Although biochemical studies have uncovered the mechanisms involved in controlling transcription at each step, how these mechanisms manifest in vivo at the level of individual genes is still unclear. Recent experimental advances have enabled single-cell measurements of RNA polymerase (RNAP) molecules engaged in the process of transcribing a gene of interest. In this article, we use Gillespie simulations to show that measurements of cell-to-cell variability of RNAP numbers and interpolymerase distances can reveal the prevailing mode of regulation of a given gene. Mechanisms of regulation at each step, from initiation to elongation dynamics, produce qualitatively distinct signatures, which can further be used to discern between them. Most intriguingly, depending on the initiation kinetics, stochastic elongation can either enhance or suppress cell-to-cell variability at the RNAP level. To demonstrate the value of this framework, we analyze RNAP number distribution data for ribosomal genes in Saccharomyces cerevisiae from three previously published studies and show that this approach provides crucial mechanistic insights into the transcriptional regulation of these genes. reserved.
DOI of Published Version
Ali MZ, Choubey S, Das D, Brewster RC. Probing Mechanisms of Transcription Elongation Through Cell-to-Cell Variability of RNA Polymerase. Biophys J. 2020 Apr 7;118(7):1769-1781. doi: 10.1016/j.bpj.2020.02.002. Epub 2020 Feb 12. PMID: 32101716; PMCID: PMC7136280. Link to article on publisher's site
Ali Z, Choubey S, Das D, Brewster RC. (2020). Probing Mechanisms of Transcription Elongation Through Cell-to-Cell Variability of RNA Polymerase. Program in Systems Biology Publications. https://doi.org/10.1016/j.bpj.2020.02.002. Retrieved from https://escholarship.umassmed.edu/sysbio_pubs/165