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Nucleic Acids Res. 2016 Jul 27;44(13):6019-35. doi: 10.1093/nar/gkw550. Epub 2016 Jun 17.

Understanding microRNA-mediated gene regulatory networks through mathematical modelling.

Author information

1
Laboratory of Systems Tumour Immunology, Department of Dermatology, Erlangen University Hospital and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, 91054, Germany xin.lai@uk-erlangen.de.
2
Department of Systems Biology & Bioinformatics, University of Rostock, Rostock, 18051, Germany Stellenbosch Institute for Advanced Study, Wallenberg Research Centre at Stellenbosch University, 7600, South Africa.
3
Laboratory of Systems Tumour Immunology, Department of Dermatology, Erlangen University Hospital and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, 91054, Germany julio.vera-gonzalez@uk-erlangen.de.

Abstract

The discovery of microRNAs (miRNAs) has added a new player to the regulation of gene expression. With the increasing number of molecular species involved in gene regulatory networks, it is hard to obtain an intuitive understanding of network dynamics. Mathematical modelling can help dissecting the role of miRNAs in gene regulatory networks, and we shall here review the most recent developments that utilise different mathematical modelling approaches to provide quantitative insights into the function of miRNAs in the regulation of gene expression. Key miRNA regulation features that have been elucidated via modelling include: (i) the role of miRNA-mediated feedback and feedforward loops in fine-tuning of gene expression; (ii) the miRNA-target interaction properties determining the effectiveness of miRNA-mediated gene repression; and (iii) the competition for shared miRNAs leading to the cross-regulation of genes. However, there is still lack of mechanistic understanding of many other properties of miRNA regulation like unconventional miRNA-target interactions, miRNA regulation at different sub-cellular locations and functional miRNA variant, which will need future modelling efforts to deal with. This review provides an overview of recent developments and challenges in this field.

PMID:
27317695
PMCID:
PMC5291278
DOI:
10.1093/nar/gkw550
[Indexed for MEDLINE]
Free PMC Article

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