Global Long Noncoding RNA Expression Profiling of MSTN and FGF5 Double-Knockout Sheep Reveals the Key Gatekeepers of Skeletal Muscle Development.

Improving livestock and poultry growth rates and increasing meat production are urgently needed worldwide. Previously, we produced a myostatin (MSTN) and fibroblast growth factor 5 (FGF5) double-knockout (MF^-/-) sheep by CRISPR Cas9 system to improve meat production, and also wool production. Both MF^-/- sheep and the F1 generation (MF^+/-) sheep showed an obvious "double-muscle" phenotype. In this study, we identified the expression profiles of long noncoding RNAs (lncRNAs) in wild-type and MF^+/- sheep, then screened out the key candidate lncRNAs that can regulate myogenic differentiation and skeletal muscle development. These key candidate lncRNAs can serve as critical gatekeepers for muscle contraction, calcium ion transport and skeletal muscle cell differentiation, apoptosis, autophagy, and skeletal muscle inflammation, further revealing that lncRNAs play crucial roles in regulating muscle phenotype in MF^+/- sheep. In conclusion, our newly identified lncRNAs may emerge as novel molecules for muscle development or muscle disease and provide a new reference for MSTN-mediated regulation of skeletal muscle development.