From mouse to human: how RNA epigenetic influences cardiomyocytes maturation to prevent cardiac hyperplasia

Tissue-specific long noncoding RNAs (lncRNA) play crucial roles in the regulation of cell growth and differentiation. Their dysregulation is often associated with neuromuscular and cardiovascular diseases, though the clear understanding of their mode of action is still incomplete. In mice, we previously identified several lncRNAs that are enriched in myogenic cells (1). In particular, Charme is highly conserved and abundant lncRNA specifically expressed in differentiated myotubes and cardiomyocytes (2). We found that during embryogenesis, the nuclear intron-retaining isoform of Charme (pCharme) acts as structural RNA by recruiting the protein Matrin3 to scaffold the formation of important nuclear condensates (3). Indeed, mice lacking pCharme develop cardiac hyperplasia due to an abnormal expression of genes involved in regulating cardiomyocytes proliferation/maturation balance (4). Intriguingly, the orthologous human transcript (hs-Charme) shares several features and a similar tissue specificity with its murine counterpart, suggesting an evolutionarily conserved function and offering intriguing possibilities for future study. Using the highly adaptable IPSCs system, we are starting to dissect hs-Charme role in the development of human cardiomyocytes. Preliminary data indicate that, in the nucleus, the transcript may play a similar role in the regulation of their maturation. As the World Health Organization classify cardiomyopathies among the most prevalent and fatal diseases in human, understanding hs-Charme involvement in cardiac development and pathologies could be extremely important, particularly in cases when a clear genetic cause was not identified.