Skeletal muscle specific overexpression of miRNA-1 impairs mechanical overload-induced skeletal muscle hypertrophy

MicroRNAs (miRNAs) are small, non-coding RNAs that play a critical role in regulating gene expression post-transcriptionally. Skeletal muscle-specific miRNAs, including miR-1, are important for skeletal muscle development and maintenance. In response to mechanical loading, skeletal muscle levels of miR-1 decrease by approximately 50%, suggesting a potential involvement in muscle hypertrophy. In the current investigation, we hypothesized that a reduction of miR-1 levels in response to mechanical loading would be necessary for skeletal muscle growth to occur. By significantly elevating miR-1 levels during the hypertrophic process via lentiviral delivery, we observed a blunted growth response in the plantaris muscle subjected to synergist ablation. A deeper RNA-based integrative analysis (transcriptomics and RNA eCLIP) indicates that miR-1 inhibits the expression of Itm2a and Melusin, two membrane-related proteins. While their exact mechanism in muscle hypertrophy is yet to be identified, our results suggest that miR-1-regulated membrane proteins are important for skeletal muscle hypertrophy. Overall design: To explore the role of miR-1 in skeletal muscle, we overexpressed miR-1 (lentivirus injection) in mice (Mimic group) that underwent 10 days of MOV-induced muscle hypertrophy. We then perform an exploratory eCLIP-seq to find out the mRNA traget of microRNA