Profiling torpor-responsive microRNAs in muscles of the hibernating primate Microcebus murinus

Abstract

When food scarcity is coupled with decreased temperatures, gray mouse lemurs (Microcebus murinus) depress their metabolic rates and retreat into bouts of either daily torpor or multi-day hibernation, without dramatically dropping body temperatures like other ‘traditional hibernators’. Rapid and reversible mechanisms are required to coordinate the simultaneous suppression of energetically expensive processes and activation of pro-survival pathways critical for successful torpor-arousal cycling. MicroRNAs, a class of endogenous non-coding small RNAs, are effective post-transcriptional regulators that modulate all aspects of cellular function. The present study hypothesizes that miRNAs are intimately involved in facilitating the molecular reorganization events necessary for lemur skeletal muscle torpor. Small RNA-Sequencing was used to compare miRNA profiles from skeletal muscles of torpid and control primates. We characterized 234 conserved miRNAs, of which 20 were differentially expressed during torpor, relative to control. Examples included downregulation of key muscle-specific (myomiR) members, miR-1 and miR-133, suggesting a switch to muscle-specific energy-saving strategies. In silico target mapping and logistic regression-based gene set analysis indicated the inhibition of energy costly pathways such as oxidative phosphorylation and muscle proliferation. The suppression of these metabolic pathways was balanced with a lack of miRNA inhibition of various signaling pathways, such as MAPK, mTOR, focal adhesion, and ErbB. This study identifies unique miRNA signatures and ‘biomarkers of torpor’ that provide us with primate-specific insights on torpor at high body temperatures that can be exploited for human biomedical concerns.