Using computer simulation models to investigate the most promising microRNAs to improve muscle regeneration during ageing

Proctor, Carole J and Goljanek-Whysall, Katarzyna ORCID: 0000-0001-8166-8800 (2017) Using computer simulation models to investigate the most promising microRNAs to improve muscle regeneration during ageing. SCIENTIFIC REPORTS, 7 (1). 12314-.

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Official URL: http://dx.doi.org/10.1038/s41598-017-12538-6

Abstract

MicroRNAs (miRNAs) regulate gene expression through interactions with target sites within mRNAs, leading to enhanced degradation of the mRNA or inhibition of translation. Skeletal muscle expresses many different miRNAs with important roles in adulthood myogenesis (regeneration) and myofibre hypertrophy and atrophy, processes associated with muscle ageing. However, the large number of miRNAs and their targets mean that a complex network of pathways exists, making it difficult to predict the effect of selected miRNAs on age-related muscle wasting. Computational modelling has the potential to aid this process as it is possible to combine models of individual miRNA:target interactions to form an integrated network. As yet, no models of these interactions in muscle exist. We created the first model of miRNA:target interactions in myogenesis based on experimental evidence of individual miRNAs which were next validated and used to make testable predictions. Our model confirms that miRNAs regulate key interactions during myogenesis and can act by promoting the switch between quiescent/proliferating/differentiating myoblasts and by maintaining the differentiation process. We propose that a threshold level of miR-1 acts in the initial switch to differentiation, with miR-181 keeping the switch on and miR-378 maintaining the differentiation and miR-143 inhibiting myogenesis.

Item Type:	Article
Uncontrolled Keywords:	Muscle, Skeletal, Cells, Cultured, Myoblasts, Animals, Mice, Inbred C57BL, Mice, MicroRNAs, Models, Animal, Regeneration, Cell Differentiation, Cell Proliferation, Gene Expression Regulation, Aging, Muscle Development, Models, Biological, Computer Simulation, Male, Gene Regulatory Networks, Sarcopenia, Primary Cell Culture, Genetic Therapy
Depositing User:	Symplectic Admin
Date Deposited:	10 Jan 2019 15:10
Last Modified:	14 Feb 2023 08:42
DOI:	10.1038/s41598-017-12538-6
Open Access URL:	https://www.nature.com/articles/s41598-017-12538-6
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3031062