ABSTRACT
Long noncoding RNAs (lncRNAs) are emerging as critical regulators of heart physiology and disease, although the studies unveiling their modes-of-action are still scarce and limited to few examples. We recently identified pCharme, a chromatin-associated lncRNA whose functional knockout in mice results in defective myogenesis and morphological remodelling of the cardiac muscle. By combining Cap-Analysis OF Gene Expression (CAGE) with single-cell (sc)RNA sequencing and whole-mount in situ hybridization analyses, here we have profiled pCharme levels and we found it expressed in cardiomyocytes since the first steps of cardiomyogenesis. At this early stage, pCharme is crucial to seed the formation of specific RNA-enriched nuclear condensates containing MATR3, its known protein interactor, as well as important regulators of cardiac development. Perturbation of this mechanism by in vivo pCharme ablation results in myocardium compaction and ventricular hypo-trabeculation due to a delayed maturation of cardiomyocytes. The identification of novel genes controlling cardiac morphology is crucially important, as in human’s congenital defects in myocardium compaction are clinically relevant and predispose patients to major complications. Our studies in vivo offer unique insights into cardiac muscle maturation and bear relevance to Charme locus for future theranostic applications.
Competing Interest Statement
The authors have declared no competing interest.
