title: Frequency modulation of stochastic gene expression bursts by strongly interacting small RNAs.
abstract: The sporadic nature of gene expression at the single-cell level-long periods of inactivity punctuated by bursts of mRNA or protein production-plays a critical role in diverse cellular processes. To elucidate the cellular role of bursting in gene expression, synthetic biology approaches have been used to design simple genetic circuits with bursty mRNA or protein production. Understanding how such genetic circuits can be designed with the ability to control burst-related parameters requires the development of quantitative stochastic models of gene expression. In this work, we analyze stochastic models for the regulation of gene expression bursts by strongly interacting small RNAs. For the parameter range considered, results based on mean-field approaches are significantly inaccurate and alternative analytical approaches are needed. Using simplifying approximations, we obtain analytical results for the corresponding steady-state distributions that are in agreement with results from stochastic simulations. These results indicate that regulation by small RNAs, in the strong interaction limit, can be used to effectively modulate the frequency of bursting. We explore the consequences of such regulation for simple genetic circuits involving feedback effects and switching between promoter states.
authors.affiliation: Department of Physics, University of Massachusetts, Boston, Massachusetts 02125, USA.
authors.forename: Niraj
authors.initials: N
authors.lastname: Kumar
authors.affiliation: College of Computer and Information Science, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jia
authors.affiliation: Department of Mathematics, University of Massachusetts, Boston, Massachusetts 02125, USA.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Zarringhalam
authors.affiliation: Department of Physics, University of Massachusetts, Boston, Massachusetts 02125, USA.
authors.forename: Rahul V
authors.initials: RV
authors.lastname: Kulkarni
mesh_terms: D005786:Gene Expression Regulation / Q000502:physiology*; D008957:Models, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D013269:Stochastic Processes
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering