细胞命运决定中ncRNA介导的调控回路建模

Modeling ncRNA-Mediated Circuits in Cell Fate Decision.

作者信息

Tian Xiao-Jun, Ferro Manuela Vanegas, Goetz Hanah

机构信息

School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.

出版信息

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

DOI:10.1007/978-1-4939-8982-9_16

PMID:30635903

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.

摘要

非编码RNA（ncRNA）在细胞命运的关键决定过程中发挥着重要作用。然而，ncRNA介导的双稳态开关背后的确切分子机制仍然难以捉摸且存在争议。近年来，系统的数学和定量实验分析在阐明控制ncRNA介导的细胞命运决定过程的分子机制方面做出了重大贡献。在本章中，我们以教学的方式回顾和总结了ncRNA数学建模的一般框架以及该一般框架在实际生物学过程中的应用。我们讨论了mRNA、miRNA和竞争性内源性mRNA（ceRNA）之间相互调节所产生的新特性，以及ncRNA数学建模在合成生物学中的作用。ncRNA与转录因子之间的正反馈环以及miRNA-mRNA相互调节产生的新特性都使双稳态开关能够指导细胞命运决定。