Novel RNA-binding activity of MYF5 enhances Ccnd1/Cyclin D1 mRNA translation during myogenesis

Nucleic Acids Research
Amaresh C PandaMyriam Gorospe

Abstract

Skeletal muscle contains long multinucleated and contractile structures known as muscle fibers, which arise from the fusion of myoblasts into multinucleated myotubes during myogenesis. The myogenic regulatory factor (MRF) MYF5 is the earliest to be expressed during myogenesis and functions as a transcription factor in muscle progenitor cells (satellite cells) and myocytes. In mouse C2C12 myocytes, MYF5 is implicated in the initial steps of myoblast differentiation into myotubes. Here, using ribonucleoprotein immunoprecipitation (RIP) analysis, we discovered a novel function for MYF5 as an RNA-binding protein which associated with a subset of myoblast mRNAs. One prominent MYF5 target was Ccnd1 mRNA, which encodes the key cell cycle regulator CCND1 (Cyclin D1). Biotin-RNA pulldown, UV-crosslinking and gel shift experiments indicated that MYF5 was capable of binding the 3' untranslated region (UTR) and the coding region (CR) of Ccnd1 mRNA. Silencing MYF5 expression in proliferating myoblasts revealed that MYF5 promoted CCND1 translation and modestly increased transcription of Ccnd1 mRNA. Accordingly, overexpressing MYF5 in C2C12 cells upregulated CCND1 expression while silencing MYF5 reduced myoblast proliferation as well as diffe...Continue Reading

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Citations

Oct 23, 2016·Free Radical Biology & Medicine·Andrea Di FrancescoRafael de Cabo
Apr 27, 2017·Nucleic Acids Research·Amaresh C PandaMyriam Gorospe
May 19, 2017·Bio-protocol·Amaresh C PandaMyriam Gorospe
May 19, 2017·Bio-protocol·Amaresh C PandaMyriam Gorospe
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Apr 4, 2021·International Journal of Molecular Sciences·Ailma O da PaixãoAlice Cristina Rodrigues
Aug 25, 2021·Journal of Cachexia, Sarcopenia and Muscle·Wen LuoXiquan Zhang

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