Characterization of the human long noncoding RNA Charme

By using a high-throughput transcriptome screening, we identified a subset of new polyadenylated and multi-exonic lncRNAs which result differentially expressed throughout murine skeletal muscle in vitro differentiation (Ballarino et al., 2015). Among them, we focused our attention on Charme (for Chromatin architect of muscle expression) which depletion in vitro impairs muscle differentiation and produces in vivo a peculiar cardiac phenotype with changes in size, structure and shape of the heart (Ballarino et al., 2018). Intriguingly, an orthologous transcript of the murine Charme (hs-Charme) was identified by a phylogenetic analysis. Similarly to the murine counterpart, hs-Charme is expressed in differentiated myotubes and its depletion affects the expression of the same subset of genes, suggesting an evolutionarily conserved function. To deepen our knowledge of Charme’s function in human, I am now producing a Charme KO iPS cell line by using the CRISPR Cas9 technology. iPS cells will be differentiated into skeletal and cardiac muscle lineages to get hints into the functional role of the human transcript. This is extremely important also considering the fact that according to the World Health Organization (WHO) cardiomyopathies are among the most frequent and fatal diseases in human.