Musashi-2 regulates skeletal muscle fiber type and energy metabolism

Introduction : Skeletal muscles are highly plastic organs, and their quantity and quality change depending on exercise, nutrition, disease, and so on.The discovery of a new master regulator of muscle mass and quality will provide new avenues for development of training methods and the prevention of muscle wasting.Musashi-2 (Msi2) is an RNA binding protein that determines neuronal cell differentiation by regulating protein translation by binding specific mRNAs.We found that Msi2 is expressed in skeletal muscle cells, higher in slow type than fast type muscles, but the role of Msi2 in skeletal muscles is unknown.The purpose of this study is to elucidate the function of Msi2 in skeletal muscle.Methods : Soleus muscles from Msi2 knock out (KO) mice were analyzed and compared to wild-type (WT) mice for biochemically and histologically.The Msi2 gene was transferred into the tibial anterior muscle by DNA electroporation method and the effect of Msi2 overexpression on energy metabolism related protein expressions was examined. Results :The soleus muscle of Msi2 KO mice was reduced in muscle mass, and whitened compared to the normal red color in WT mice.Histological analysis revealed that the number of type IIa fibers, which are of the fast type but have high metabolic capacity, was reduced in KO mice.The contractile force of isolated soleus muscle was lower in KO mice.Mitochondrial protein marker (COX IV) and myoglobin were decreased in soleus of Msi2 KO mice, whereas Msi2 overexpression increased COX IV and myoglobin in tibial anterior muscles.Conclusions : Msi2 regulates skeletal muscle mass and quality, in particular the maintenance of type IIa fibers and the expression of energy metabolism-related proteins.Msi2 is an element to control the homeostasis of skeletal muscle and could be a molecular target to enhance muscle strength and treat muscle atrophy.