mRNA-miRNA Reciprocal Regulation Enabled Bistable Switch Directs Cell Fate Decision

Abstract

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.

32 pages, 5 figures and 7 supporting figures in FEBS Letters, 2016

References in corpus (2)

• Statistical Mechanics Model for the Dynamics of Collective Epigenetic Histone Modification
• RNA-based regulation: dynamics and response to perturbations of competing RNAs

Cited by in corpus (2)

• Investigating Epithelial-To-Mesenchymal Transition with Integrated Computational and Experimental Approaches
• Competing endogenous RNA crosstalk at system level