The lncRNA Charme, an evolutionary conserved regulator of muscle differentiation and pathology

Tissue-specific long noncoding RNAs (lncRNA) play essential roles in regulating cell growth, differentiation and physiology, although the knowledge concerning their mechanisms of action is still far from complete. Among them, nuclear lncRNAs are generally associated with chromatin and can contribute to the formation of higher-order tridimensional structures. Their dysregulation was often linked with several pathological states, including neuromuscular and cardiovascular diseases. As such, 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) where it acts as an “architect” RNA to scaffold the formation of physiologically important nuclear condensates. Indeed, mice lacking Charme develop muscle hyperplasia due to an abnormal expression of genes involved in muscle cell proliferation/maturation balance (3). 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. Accordingly, we found that HSCHARME expression is significantly altered across patients affected by several cardiomyopathies and impinges on pathology-associated pathways. Overall, our data highlight the crucial role of the lncRNA HSCHARME in human muscle physiology and pathology.