MicroRNA Based Feedforward Control of Intrinsic Gene Expression Noise.

Abstract

Intrinsic noise, which arises in gene expression at low copy numbers, can be controlled by diverse regulatory motifs, including feedforward loops. Here, we study an example of a feedforward control system based on the interaction between an mRNA molecule and an antagonistic microRNA molecule encoded by the same gene, aiming to quantify the variability (or noise) in molecular copy numbers. Using linear noise approximation, we show that the mRNA noise is sub-Poissonian in case of non-bursty transcription, and exhibits a nonmonotonic response both to the species natural lifetime ratio and to the strength of the antagonistic interaction. Additionally, we use the Chemical Reaction Network Theory to prove that the mRNA copy number distribution is Poissonian in the absence of spontaneous mRNA decay channel. In case of transcriptional bursts, we show that feedforward control can attenuate the super-Poissonian gene-expression noise that is due to bursting, and that the effect is more considerable at the protein than at the mRNA level. Our results indicate that the strong coupling between mRNA and microRNA in the sense of burst stoichiometry and also of timing of production events renders the microRNA based feedforward motif an effective mechanism for the control of gene expression noise.