Mathematical modelling of a microRNA-regulated gene network in Caenorhabditis elegans
| Autor: | John R. King, Simon Preston, David I. de Pomerai, Mainul Haque, Matthew Loose |
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| Rok vydání: | 2020 |
| Předmět: |
Bistability
biology Applied Mathematics 05 social sciences Gene regulatory network Translation (biology) 02 engineering and technology General Medicine Computational biology biology.organism_classification Computational Mathematics Modeling and Simulation 0502 economics and business microRNA Gene expression 0202 electrical engineering electronic engineering information engineering 020201 artificial intelligence & image processing General Agricultural and Biological Sciences Gene Heterochrony 050203 business & management Caenorhabditis elegans |
| Zdroj: | Mathematical Biosciences and Engineering. 17:2881-2904 |
| ISSN: | 1551-0018 |
| DOI: | 10.3934/mbe.2020162 |
| Popis: | MicroRNAs are known to regulate gene expression either by repressing translation or by directing sequence-specific degradation of target mRNAs, and are therefore considered to be key regulators of gene expression. A gene-regulatory pathway involving heterochronic genes controls the temporal pattern of Caenorhabditis elegans postembryonic cell lineages. Based on experimental data, we propose and analyze a mathematical model of a gene-regulatory module in this nematode involving two heterochronic genes, lin-14 and lin-28, which are both regulated by lin-4, encoding a microRNA. The conditions under which the model experiences bifurcations are investigated. We determine the parameter regimes for which the system exhibits monostability and bistability, the latter associated with a biological switch. We observe in particular that bistability occurs without co-operativity, in keeping with knowledge about the regulatory behaviour of lin-14 and lin-28. The analytical results are confirmed by numerical simulations that illustrate how the microRNA lin-4 plays a crucial role in determining of the qualitative dynamics of the model. |
| Databáze: | OpenAIRE |
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