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RESEARCH PRODUCT

Physical activity responsive miRNAs – Potential mediators of training responses in human skeletal muscle?

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1. The basics of miRNA-mediated regulation The plasticity of skeletal muscle is of utmost importance for responding to and coping with environmental demands that emerge from changes in physical activity patterns, nourishment, hormonal status, and health. As is well known, a sedentary lifestyle, aging, immobilization, and chronic diseases are associated with reduced muscle mass and function, while regular exercise improves muscle function and reduces the rate of decrement throughout life. 1 However, we do not have a complete understanding of the molecular factors controlling skeletal muscle adaptation to exercise stimuli. Recently identified microRNA molecules (miRNAs) have rapidly gained attention within the scientific community as modulators of muscle properties and potential therapeutic targets. 2 miRNAsdshort, conserved, non-protein-coding RNA molecules capable of repressing gene expression in a sequence-specific manner 3 dare found in a wide variety of life forms. Some miRNAs show cell type- or tissue-specific expression patterns, while others are expressed ubiquitously. Typically, miRNAs have intra- or autocrine functions, but they are also found in all body fluids. Currently it is not clear if miRNAs are actively secreted to the circulation to deliver endocrine functions, or whether they are passively released following cell damage. In short, miRNA-mediated regulation is complicated. miRNAs form regulatory networks in which one miRNA can modulate the expression of several targets, and each miRNA is regulated by other miRNAs or transcription factors. Furthermore, miRNAs are responsive to extracellular stimuli, such as physical exercise, steroid hormones, and nutritional factors. The miRNAs most abundantly found in cardiac and skeletal muscle are named myomiRs. 4 In addition to the regulation of muscle properties by exerciseresponsive myomiRs, other muscle tissue-expressed miRNAs are likely to contribute to the plasticity of skeletal muscle, for example, in response to sex steroid hormones.