title: Reciprocal regulation between mRNA and microRNA enables a bistable switch that directs cell fate decisions.
abstract: Micro RNAs (miRNAs) serve as crucial post-transcriptional regulators in a variety of essential cell fate decisions. However, the contribution of mRNA-miRNA mutual regulation to bistability is not fully understood. In the present study, we built a set of mathematical models of mRNA-miRNA interactions and systematically analyzed the sensitivity of the response curves under various conditions. Our findings indicate that mRNA-miRNA reciprocal regulation could manifest ultrasensitivity to subserve the generation of bistability when equipped with a positive feedback loop. We also find that the region of bistability is expanded by a stronger competing endogenous mRNA. Interestingly, bistability can be generated without a feedback loop if multiple miRNA binding sites exist on a target mRNA. Thus, we demonstrate the importance of simple mRNA-miRNA reciprocal regulation in cell fate decisions.
authors: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, PA, USA. xjtian@pitt.edu.
authors: Xiao-Jun
authors: http://orcid.org/0000-0002-5601-2057
authors: XJ
authors: Tian
authors: Genetics, Bioinformatics and Computational Biology Program, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors: Hang
authors: H
authors: Zhang
authors: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, PA, USA.
authors: Jingyu
authors: J
authors: Zhang
authors: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, PA, USA. xing1@pitt.edu.|Computational Science Research Center, Beijing, China. xing1@pitt.edu.
authors: Jianhua
authors: J
authors: Xing
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: bistability; ceRNA; cell fate decision; reciprocal regulation; recycle ratio; ultrasensitivity