MicroRNA-99b-5p downregulates protein synthesis in human primary myotubes

• Published in: American Journal of Physiology: Cell Physiology Vol. 319; no. 2; pp. C432 - C440
• Main Authors: Zacharewicz, Evelyn, Kalanon, Ming, Murphy, Robyn M., Russell, Aaron P., Lamon, Séverine
• Format: Journal Article
• Language: English
• Published: 01.08.2020
• ISSN: 0363-6143; 1522-1563; 1522-1563
• DOI: 10.1152/ajpcell.00172.2020

microRNAs (miRNAs) are important regulators of cellular homeostasis and exert their effect by directly controlling protein expression. We have previously reported an age-dependent negative association between microRNA-99b (miR-99b-5p) expression and muscle protein synthesis in human muscle in vivo. Here we investigated the role of miR-99b-5p as a potential negative regulator of protein synthesis via inhibition of mammalian target for rapamycin (MTOR) signaling in human primary myocytes. Overexpressing miR-99b-5p in human primary myotubes from young and old subjects significantly decreased protein synthesis with no effect of donor age. A binding interaction between miR-99b-5p and its putative binding site within the MTOR 3′-untranslated region (UTR) was confirmed in C 2 C 12 myoblasts. The observed decline in protein synthesis was, however, not associated with a suppression of the MTOR protein but of its regulatory associated protein of mTOR complex 1 (RPTOR). These results demonstrate that modulating the expression levels of a miRNA can regulate protein synthesis in human muscle cells and provide a potential mechanism for muscle wasting in vivo.