MicroRNA, Myostatin, and Metabolic Rate Depression: Skeletal Muscle Atrophy Resistance in Hibernating Myotis lucifugus.

Little brown bats (Myotis lucifugus) cluster in hibernacula sites over winter, in which they use metabolic rate depression (MRD) to facilitate entrance and exit of hibernation. This study used small RNA sequencing and bioinformatic analyses to identify differentially regulated microRNAs (miRNAs) and to predict their downstream effects on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms in the skeletal muscle of torpid M. lucifugus as compared to euthermic controls. We observed a subset of ten miRNAs whose expression changed during hibernation, with predicted functional roles linked to cell cycle processes, downregulation of protein degradation via ubiquitin-mediated proteolysis, downregulation of signaling pathways, including MAPK, p53, mTOR, and TGFβ, and downregulation of cytoskeletal and vesicle trafficking terms. Taken together, our results indicate miRNA regulation corresponding to both widely utilized MRD survival strategies, as well as more hibernation- and tissue-specific roles in M. lucifugus, including skeletal muscle atrophy resistance via myostatin inhibition and insulin signaling suppression.