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

Lookup NU author(s): Dr Carole Proctor

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2017 The Author(s). 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.


Publication metadata

Author(s): Proctor CJ, Goljanek-Whysall K

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2017

Volume: 7

Issue: 1

Online publication date: 26/09/2017

Acceptance date: 05/09/2017

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41598-017-12538-6

DOI: 10.1038/s41598-017-12538-6


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