Modeling ncRNA-Mediated Circuits in Cell Fate Decision

Methods Mol Biol. 2019:1912:411-426. doi: 10.1007/978-1-4939-8982-9_16.

Abstract

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 on 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 on real biological processes. We discuss the emerging properties resulting from the reciprocal regulation between mRNA, miRNA, and competing endogenous mRNA (ceRNA), as well as the role of mathematical modeling of ncRNA in synthetic biology. 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 decision.

Keywords: Bistability; Cell fate decision; Competing endogenous mRNA; Mathematical modeling; Posttranscriptional; Ultrasensitivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Computational Biology / instrumentation
  • Computational Biology / methods*
  • Feedback, Physiological
  • Gene Regulatory Networks
  • Humans
  • Models, Genetic*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • Synthetic Biology

Substances

  • RNA, Messenger
  • RNA, Untranslated