Several studies pointed out the relevance of extrinsic noise in molecular networks in shaping cell decision making and differentiation . Interestingly, bimodal distributions of gene expression levels, that may be a feature of phenotypic differentiation, are a common phenomenon in gene expression data. The modes of the distribution often correspond to different physiological states of the system. In this work we address the role of extrinsic noise in shaping bimodal gene distributions in the context of microRNA (miRNA)-mediated regulation , both with stochastic modelling and simulations . MiRNAs are small noncoding RNA molecules that downregulate the expression of their target mRNAs. The titrative nature of the interaction is sufficient to induce bimodal distributions of the targets. We study the fluctuating miRNA transcription case to probe the effects of  extrinsic noise on the system . We show that (i) bimodal target distributions can be obtained exploiting a noisy environment even in case of small miRNA-target interaction strength , (ii) an increase in the extrinsic noise shifts the range of target transcription rates that allow bimodality towards higher values, (iii) the protein half-life may buffer bimodal mRNA preventing its distribution from becoming bimodal and that (iv) in a noisy environment different targets may cross-regulate each other's bimodal distribution when competing for a shared pool of miRNAs even if the miRNA regulation is small .
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 .
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titrative nature of the interaction is sufficient to induce bimodal distributions of the targets. We study the fluctuating miRNA transcription case to probe the effects
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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
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by introducing a fluctuating miRNA-transcription rate. We find that the presence of extrinsic noise favours the presence of
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which can be observed for a wider range of parameters compared to the case with intrinsic noise only and for lower
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, (ii) an increase in the extrinsic noise shifts the range of target transcription rates that allow bimodality towards higher values, (iii) the protein
. 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
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may buffer bimodal mRNA preventing its distribution from becoming bimodal and that (iv) in a noisy environment different targets may cross-regulate each other's bimodal distribution when competing for a shared pool of miRNAs even if the miRNA regulation is small