miR-378 and its host gene Ppargc1β exhibit independent expression in mouse skeletal muscle

MicroRNAs (miRNAs) are implicated in multiple biological processes in physiological and pathological settings. Nearly half of the known miRNAs are classified as 'intronic' miRNAs because they are embedded within the introns of protein-coding or noncoding genes. Such miRNAs were thought to be processed from primary host gene transcripts and share the promoter of their host. Recent analyses predicted that some intronic miRNAs might be transcribed and regulated as independent units, but there is little direct evidence for this in a specific biological context. Here, we focused on miR-378, which is located within the first intron of the peroxisome proliferator-activated receptor γ coactivator 1-beta (Ppargc1β) gene and critically regulates skeletal muscle cell differentiation and muscle regeneration. We demonstrate that miR-378 and Ppargc1β exhibit distinct expression patterns during skeletal muscle cell differentiation. In terminally differentiated adult skeletal muscle tissues of mice, miR-378 is predominantly expressed in glycolytic muscle, whereas Ppargc1β is mainly expressed in oxidative soleus muscle. Mechanistically, miR-378, but not Ppargc1β, is regulated by the transcription factor, MyoD, in muscle cells. Our findings identify a regulatory model of miR-378 expression, thereby helping us to understand its physiological function in skeletal muscle.