The long noncoding RNA MyHC IIA/X-AS contributes to skeletal muscle myogenesis and maintains the fast fiber phenotype.

Mammalian skeletal muscles comprise different types of muscle fibers, and this muscle fiber heterogeneity is generally characterized marked by the expression of myosin heavy chain (MyHC) isoforms. A switch in MyHC expression leads to muscle fiber type transition under various physiological and pathological conditions, but the underlying regulatory coordinating the switch of MyHC expression remain largely unknown. Experiments reported in the present study revealed the presence of an skeletal muscle-specific antisense transcript generated from the intergenic region between porcine MyHC IIa and Iix and is referred to here as MyHC IIA/X-AS. We found that MyHC IIA/X-AS is identified as a long noncoding RNA (lncRNA) that is strictly expressed in skeletal muscles and predominantly distributed in the cytoplasm. Genetic analysis disclosed that MyHC IIA/X-AS stimulates cell cycle exit of skeletal satellite cells and their fusion into myotubes. Moreover, we observed that MyHC IIA/X-AS is more enriched in fast-twitch muscle and represses slow-type gene expression and thereby maintains the fast phenotype. Furthermore, we found that MyHC IIA/X-AS acts as a competing endogenous RNA (ceRNA) that sponges microRNA-130b (miR-130b) and thereby maintains MyHC IIx expression and the fast fiber muscle. We also noted that miR-130b was proved to down-regulates MyHC IIx by directly targeting its 3'-UTR. Together, the results of our study uncovered a novel pathway, which revealed that an lncRNA derived from the skeletal MyHC cluster could modulates local MyHC expression in trans, highlighting the role of lncRNAs in muscle fiber type switching.