文献类型：期刊文献

英文题名：A Stochastic Model of Gene Expression with Polymerase Recruitment and Pause Release

作者：Cao, Zhixing[1,2,5];Filatova, Tatiana[2,4];Oyarzun, Diego A.[2,3];Grima, Ramon[2]

机构：[1]East China Univ Sci & Technol, Key Lab Adv Control & Optimizat Chem Proc, Minist Educ, Shanghai, Peoples R China;[2]Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland;[3]Univ Edinburgh, Sch Informat, Edinburgh, Midlothian, Scotland;[4]Univ Edinburgh, Sch Math, Edinburgh, Midlothian, Scotland;[5]Tongji Univ, Shanghai Inst Intelligent Sci & Technol, Shanghai, Peoples R China

年份：2020

卷号：119

期号：5

起止页码：1002

外文期刊名：BIOPHYSICAL JOURNAL

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000565024300012)】；

基金：Z.C. gratefully acknowledges support of the UK Research Councils Synthetic Biology for Growth programme and of the Biotechnology and Biological Sciences Research Council, Engineering and Physical Sciences Research Council, and Medical Research Council (B/M018040/1) and careful proofreading by J. Holehouse. R.G. acknowledges support from Biotechnology and Biological Sciences Research Council grant BB/M025551/1. D.O. acknowledges support from the Human Frontier Science Program (grant RGY076/2015).

语种：英文

摘要：Transcriptional bursting is a major source of noise in gene expression. The telegraph model of gene expression, whereby transcription switches between on and off states, is the dominant model for bursting. Recently, it was shown that the telegraph model cannot explain a number of experimental observations from perturbation data. Here, we study an alternative model that is consistent with the data and which explicitly describes RNA polymerase recruitment and polymerase pause release, two steps necessary for messenger RNA (mRNA) production. We derive the exact steady-state distribution of mRNA numbers and an approximate steady-state distribution of protein numbers, which are given by generalized hypergeometric functions. The theory is used to calculate the relative sensitivity of the coefficient of variation of mRNA fluctuations for thousands of genes in mouse fibroblasts. This indicates that the size of fluctuations is mostly sensitive to the rate of burst initiation and the mRNA degradation rate. Furthermore, we show that 1) the time-dependent distribution of mRNA numbers is accurately approximated by a modified telegraph model with a Michaelis-Menten like dependence of the effective transcription rate on RNA polymerase abundance, and 2) the model predicts that if the polymerase recruitment rate is comparable or less than the pause release rate, then upon gene replication, the mean number of RNA per cell remains approximately constant. This gene dosage compensation property has been experimentally observed and cannot be explained by the telegraph model with constant rates.