Modeling ncRNA-Mediated Circuits in Cell Fate Decision: From Systems Biology to Synthetic Biology.

Noncoding RNAs (ncRNAs) play critical roles in essential cell fate decisions. However, the exact molecular mechanisms underlying ncRNA-mediated bistable switches remain elusive and controversial. In recent years, systematic mathematical and quantitative experimental analyses have made significant contributions to elucidating the molecular mechanisms of controlling ncRNA-mediated cell fate decision processes. In this chapter, we review and summarize the general framework of mathematical modeling of ncRNA in a pedagogical way and the application of this general framework to real biological processes. We discuss the emerging properties resulting from the reciprocal regulation between mRNA, miRNA, and competing endogenous mRNA (ceRNA). We also explore the efforts within the synthetic biology approach to understand the fundamental design principles underlying cell fate decisions. Both the positive feedback loops between ncRNAs and transcription factors and the emerging properties from the miRNA-mRNA reciprocal regulation enable bistable switches to direct cell fate decisions.