The nuclear lncRNA Charme plays an evolutionarily conserved role in the epigenetic regulation of muscle differentiation

Tissue-specific long noncoding RNAs (lncRNA) play pivotal roles in cell physiology and development, although the knowledge concerning their mechanisms of action is still far from complete. Their dysregulation was linked with several pathological states including cardiovascular diseases, that represent the primary cause of death worldwide, due to the limited regenerative abilities of the adult heart. Understanding their role in muscle development and pathologies is extremely important, particularly in cases when a clear genetic cause was not identified. In mice, we recently characterized Charme, a highly conserved and abundant lncRNA specifically expressed in the nucleus of differentiated myotubes and cardiomyocytes (1,2). We found that mice lacking Charme develop muscle hyperplasia due to an abnormal expression of genes involved in muscle cell proliferation/maturation balance (3). In the heart, this alteration leads to a morphological remodelling and functional impairment of the cardiac muscle. Intriguingly, the orthologous human transcript (HSCHARME) shares several features and a similar tissue specificity with its murine counterpart, suggesting an evolutionarily conserved function and offering intriguing possibilities for future studies. For instance, HSCHARME could serve as a model to explore the interplay between muscle and neuronal lncRNAs in neuromuscular development and diseases as well as heart development and cardiomyopathies. Indeed, we found that HSCHARME expression is significantly altered across patients affected by several cardiomyopathies and impinges on pathology-associated pathways. Overall, our data highlight a crucial role for the lncRNA HSCHARME in human muscle physiology and pathology and identify potential targets of disease.