Document Type

Article

Publication Date

9-27-2019

Keywords

JGM

JAX Source

J R Soc Interface 2019 Sep 27; 16(158):20190437

Volume

16

Issue

158

First Page

20190437

Last Page

20190437

ISSN

1742-5662

PMID

31551049

DOI

https://doi.org/10.1098/rsif.2019.0437

Grant

US Army Research Office W911NF-14-1-0486

Abstract

MicroRNAs form a class of short, non-coding RNA molecules which are essential for proper development in tissue-based plants and animals. To help explain their role in gene regulation, a number of mathematical and computational studies have demonstrated the potential canalizing effects of microRNAs. However, such studies have typically focused on the effects of microRNAs on only one or a few target genes. Consequently, it remains unclear how these small-scale effects add up to the experimentally observed developmental outcomes resulting from microRNA perturbation at the whole-genome level. To answer this question, we built a general computational model of cell differentiation to study the effect of microRNAs in genome-scale gene regulatory networks. Our experiments show that in large gene regulatory networks, microRNAs can control differentiation time without significantly changing steady-state gene expression profiles. This temporal regulatory role cannot be naturally replicated using protein-based transcription factors alone. While several microRNAs have been shown to regulate differentiation time

Comments

We thank Paola Vera-Licona, Pedro Mendes, and Jeff Chuang for valuable discussions and feedback on the manuscript.

Open access under the terms of the Creative Commons Attribution License

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