microRNA-151-3p regulates slow muscle gene expression by targeting ATP2a2 in skeletal muscle cells.

MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate the stability or translation of cognate mRNAs at the post-transcriptional level. Accumulating evidence indicates that miRNAs play important roles in many aspects of muscle function, including muscle growth and development, regeneration, contractility, and muscle fiber type plasticity. In the current study, we examined the function of miR-151-3p in myoblast proliferation and differentiation. Results show that overexpression of miR-151-3p not only upregulates myoblast proliferation, but also decreases slow muscle gene expression (such as MHC-β/slow and slow muscle troponin I) in both C2C12 myotubes and in primary cultures. Alternatively, inhibition of miR-151-3p by antisense RNA was found to upregulate MHC-β/slow expression, indicating that miR-151-3p plays a role in muscle fiber type determination. Further investigation into the underlying mechanisms revealed for the first time that miR-151-3p directly targets ATP2a2, a gene encoding for a slow skeletal and cardiac muscle specific Ca(2+) ATPase, SERCA2 thus downregulating slow muscle gene expression. Mechanisms by which the alteration in SERCA2 expression induces changes in other slow muscle gene expression levels needs to be defined in future research.