Abstract
MicroRNAs are small regulatory noncoding RNAs that repress gene expression at the posttranscriptional level. Previous studies have reported that the expression of miR-23, miR-27, and miR-24, driven from two miR-23–27–24 clusters, is altered by various pathophysiological conditions. However, their functions in skeletal muscle have not been clarified. To define the roles of the miR-23–27–24 clusters in skeletal muscle, we generated double-knockout (dKO) mice muscle-specifically lacking the miR-23–27–24 clusters. The dKO mice were viable and showed normal growth. The contractile and metabolic features of the muscles, represented by the expression of the myosin heavy chain and the oxidative markers PGC1-α and COX IV, were not altered in the dKO mice compared with wild-type mice. The dKO mice showed increased cross-sectional areas of the oxidative fibers. However, this dKO did not induce functional changes in the muscles. The dKO mice also showed normal adaptation to voluntary wheel running for 4 weeks, including the glycolytic-to-oxidative fiber type switch, and increases in mitochondrial markers, succinate dehydrogenase activity, and angiogenesis. In conclusion, our data demonstrate that the miR-23–27–24 clusters have subtle effects on skeletal muscle development and endurance-exercise-induced muscle adaptation.
Highlights
MicroRNAs are short noncoding RNAs that negatively regulate gene expression at the posttranscriptional level[1]
We have demonstrated that Ckmm-cre induced the ablation of the miR-23a/b clusters, which did not produce a significant skeletal muscle phenotype, either in the resting or exercised state
The distributions of cross sectional areas (CSAs) of the type I, type IIa, and type IId/x fibers were larger than in the WT (Fig. 3I). This suggests that the absence of the miR-23a/b clusters more strongly affected the phenotype of the oxidative fibers than that of the glycolytic fibers because the expression of the miR-23a/b clusters is greater in the soleus than in the plantaris[16,27]
Summary
MicroRNAs (miRNAs) are short noncoding RNAs that negatively regulate gene expression at the posttranscriptional level[1]. A number of studies have reported that the miRNAs in the miR-23–27–24 clusters are altered in response to physiological and/or pathological changes in the skeletal muscle. Numerous studies have reported that miRNA expression in skeletal muscle is altered by various types of exercise[21], and have suggested that these changes in miRNAs contribute to the beneficial effects of exercise[22,23]. We examined the changes in the skeletal muscle phenotypes of the knockout mice in response to endurance exercise. This is the first study to report the muscle-specific loss of function of the miR-23–27–24 clusters in vivo
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