  Several studies highlighted the relevance of extrinsic noise in shaping cell
decision making and differentiation in molecular networks. Experimental
evidences of phenotypic differentiation are given by the presence of bimodal
distributions of gene expression levels, where the modes of the distribution
often correspond to different physiological states of the system. We
theoretically address the presence of bimodal phenotypes in the context of
microRNA (miRNA)-mediated regulation. MiRNAs are small noncoding RNA molecules
that downregulate the expression of their target mRNAs. The nature of this
interaction is titrative and induces a threshold effect: below a given target
transcription rate no mRNAs are free and available for translation. We
investigate the effect of extrinsic noise on the system by introducing a
fluctuating miRNA-transcription rate. We find that the presence of extrinsic
noise favours the presence of bimodal target distributions which can be
observed for a wider range of parameters compared to the case with intrinsic
noise only and for lower miRNA-target interaction strength. Our results suggest
that combining threshold-inducing interactions with extrinsic noise provides a
simple and robust mechanism for obtaining bimodal populations not requiring
fine tuning. We furthermore characterise the protein distributions dependence
on protein half-life.

Molecular Networks