BackgroundMiRNAs are essential regulators of skeletal muscle development and homeostasis. To date, the role and regulation of miRNAs in myogenesis have been mostly studied in tissue culture and during embryogenesis. However, little information relating to miRNA regulation during early post-natal skeletal muscle growth in mammals is available. Using a high-throughput miRNA qPCR-based array, followed by stringent statistical and bioinformatics analysis, we describe the expression pattern and putative role of 768 miRNAs in the quadriceps muscle of mice aged 2 days, 2 weeks, 4 weeks and 12 weeks.ResultsForty-six percent of all measured miRNAs were expressed in mouse quadriceps muscle during the first 12 weeks of life. We report unprecedented changes in miRNA expression levels over time. The expression of a majority of miRNAs significantly decreased with post-natal muscle maturation in vivo. MiRNA clustering identified 2 subsets of miRNAs that are potentially involved in cell proliferation and differentiation, mainly via the regulation of non-muscle specific targets.ConclusionCollective miRNA expression in mouse quadriceps muscle is subjected to substantial levels of regulation during the first 12 weeks of age. This study identified a new suite of highly conserved miRNAs that are predicted to influence early muscle development. As such it provides novel knowledge pertaining to post-natal myogenesis and muscle regeneration in mammals.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3399-2) contains supplementary material, which is available to authorized users.
MicroRNAs (miRNAs) undergo high levels of regulation in skeletal muscle development and control skeletal muscle mass, function and metabolism over the lifespan. More recently, the role of long non-coding RNAs (lncRNAs) in skeletal muscle regulation has started to emerge. Following up on our recent study describing the expression pattern and putative roles of 768 miRNAs in the quadriceps muscle of mice at early life stages, we used a high-throughput miRNA qPCR-based array to assess the expression of the same miRNAs in 28-month old male mouse quadriceps muscle. In addition, we report the expression patterns of lncRNAs playing a putative role in muscle development and adaptation from growth to old age. Twelve miRNAs were significantly downregulated in 28-month old muscle when compared with 12-week old muscle. Ten of them clustered at the Dlk1-Dio3 locus, known as ‘Callipyge,’ which is associated with muscle development and hypertrophy. This collective downregulation was paralleled by decreases in the expression levels of the maternally expressed imprinted LncRNA coding genes Meg3 and Rian stemming from the same chromosomal region. In contrast, the paternally expressed imprinted Dlk1-Dio3 locus members Rtl1, Dio3, and Dlk1 and the muscle related lncRNAs lncMyoD1, Neat_v1, Neat_v2, and Malat1 underwent significant changes during growth, but their expression levels were not altered past the age of 12 weeks, suggesting roles limited to hyperplasia and early hypertrophy. In conclusion, collective muscle miRNA expression gradually decreases over the lifespan and a cluster of miRNAs and maternally expressed lncRNAs stemming from the Callipyge locus is significantly dysregulated in aging muscle. The Dlk1-Dio3 locus therefore represents a potential new mechanism for age-related muscle decline.
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