Probing Mechanisms of Transcription Elongation Through Cell-to-Cell Variability of RNA Polymerase
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UMass Chan Affiliations
Department of Microbiology and Physiological SystemsProgram in Systems Biology
Document Type
Journal ArticlePublication Date
2020-04-07Keywords
Biochemical Phenomena, Metabolism, and NutritionBiochemistry, Biophysics, and Structural Biology
Cell and Developmental Biology
Enzymes and Coenzymes
Systems Biology
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Show full item recordAbstract
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.Source
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
DOI
10.1016/j.bpj.2020.02.002Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49895PubMed ID
32101716Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.bpj.2020.02.002