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

journal contribution
posted on 01.08.2020, 00:00 authored by E Zacharewicz, M Kalanon, R M Murphy, Aaron RussellAaron Russell, Severine LamonSeverine Lamon
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 C2C12 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.

History

Journal

American journal of physiology. Cell physiology

Volume

319

Issue

2

Pagination

C432 - C440

Publisher

American Physiological Society

Location

Bethesda, Md.

ISSN

0363-6143

eISSN

1522-1563

Language

eng

Publication classification

C1 Refereed article in a scholarly journal