miRNAs serve as crucial post-transcriptional regulators of gene expression. Recent experimental studies report that an miRNA and its target mRNA reciprocally regulate each other and miRNA is recycled with a ratio upon degradation of mRNA-miRNA complex. The functionality of this mutual regulation and dynamic consequences of miRNA recycling are not fully understood. Here, we built a set of mathematical models of mRNA-miRNA interactions and systematically analyzed their dynamical responses under various conditions. First, we found that mRNA-miRNA reciprocal regulation manifests great versatility, such as subsensitive activation, ultrasensitive and subsensitive inhibition, depending on parameters such as the miRNA recycle ratio and the mRNA-miRNA complex degradation rate constant. Second, ultrasensitivity from reciprocal mRNA-miRNA regulation contributes to generation of bistability . Furthermore, the degree of ultrasensitivity is amplified by a stronger competing mRNA (ceRNA). Last, multiple miRNA binding sites  on a target mRNA leads to emergence of nonmonotonic dual response (duality) and bistability even in the absence of any imposed feedback regulation . Thus, we demonstrated several novel functionalities that can be generated from simple mRNA-miRNA reciprocal regulation , in addition to canonical miRNA mediated degradation and translational repression of mRNA. Quantitative experiments are suggested to test the model predictions .
miRNAs serve as crucial post-transcriptional regulators in various essential cell fate decision. However, the contribution of the mRNA-miRNA mutual regulation to bistability is not fully understood. Here, we built a set of mathematical models of mRNA-miRNA interactions and systematically analyzed the sensitivity of response curves under various conditions. First, we found that mRNA-miRNA reciprocal regulation could manifest ultrasensitivity to subserve the generation of bistability when equipped with a positive feedback loop. Second, the region of bistability is expanded by a stronger competing mRNA (ceRNA). Interesting, bistability can be emerged without feedback loop if multiple miRNA binding sites exist on a target mRNA . Thus, we demonstrated the importance of simple mRNA-miRNA reciprocal regulation in cell fate decision .
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