The process of muscle differentiation (myogenesis) involves the transformation and rearrangement of proliferative, quiescent myogenic progenitors (myoblasts) into multinucleated myotubes. This involves significant changes in gene expression, as well as enhanced ribosome biogenesis required for the increased demand for protein synthesis. Given that nucleolar morphology is coupled to altered gene expression, in this study, Miyake and McDermott (Miyake and McDermott, 2023) assess changes in nucleolar morphology during myogenesis. Here, using immunofluorescence analysis, the authors show that myoblasts contain multiple small spherical nucleoli, whereas multinucleated myotubes have one large, and often irregularly shaped, nucleolus. This nucleolar re-organisation is associated with increased ribosomal RNA (rRNA) production and protein translation in myotubes. Additionally, as mTOR is known to regulate ribosome biogenesis and translation, the authors hypothesised that it might regulate these nucleolar events. Indeed, they found that inhibition of mTOR with rapamycin attenuated nucleolar changes during myogenesis, and conversely, hyperactivation of mTOR exacerbated these phenotypes. Together, these findings demonstrate the coupling of nucleolar morphology to changes in translation and ribosome biogenesis during myogenic differentiation and identify mTOR signalling as a regulator of this process.
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