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Background Information Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a master regulator of cell and whole-body energy homoeostasis. REV-ERB alpha is a nuclear receptor that plays an important role in metabolism. While mTORC1 activation is necessary for muscle differentiation, the role of REV-ERB alpha is less clear. Results We studied the effect of REV-ERB alpha overexpression and silencing as well as mTORC1 activation and inhibition on the differentiation of C2C12 myoblasts to myotubes. mTOR, myogenin and REV-ERB alpha were induced during differentiation of myoblasts into myotubes. REV-ERB alpha was found to activate mTORC1 during the differentiation process even in the absence of the differentiation medium. This activation was presumably through the downregulation of the expression of TSC1, an mTORC1 inhibitor. Conclusion Herein we show that REV-ERB alpha promotes myoblasts differentiation via the activation of the mTORC1 signalling pathway. Significance REV-ERB alpha modulation can activate mTORC1 signalling and promote myoblasts differentiation.