Stress responsive miR-23a attenuates skeletal muscle atrophy by targeting MAFbx /atrogin-1

Abstract

Muscle atrophy occurs in many pathological states and results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. We used dexamethasone to induce muscle wasting and investigated the role of a microRNA (miRNA) in the control of muscle-specific E3 ubiquitin ligase MAFbx/atrogin-1. Here we show that miR-23a suppresses MAFbx/atrogin-1 translation by binding to 3'UTR of the mRNA. Furthermore, ectopic expression of miR-23a is sufficient to protect myocytes from atrophy in vitro and in vivo in response to dexamethasone treatment, and heat stress-induced miR-23a protects muscle from dexamethasone-induced muscle atrophy. Our surprising discovery of the physiological role of miR-23a in preventing the atrophy program should lay the basis not only for further understanding of the mechanisms of muscle wasting in diverse diseases, but also for developing novel therapies for these debilitating conditions.