期刊
ELIFE
卷 12, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.81360
关键词
ncRNA; lncRNA; cardiomyogenesis; heart; muscle; development; Mouse
类别
Long noncoding RNAs (lncRNAs) play a critical role in heart physiology and disease. We identified a lncRNA called pCharme that is associated with chromatin and is involved in myogenesis and cardiac muscle remodeling in mice. Through various molecular analyses, we found that pCharme is specifically expressed in cardiomyocytes and is important for their maturation and cardiac development. The loss of pCharme leads to delayed cardiomyocyte maturation and morphological alterations in the ventricular myocardium. This study provides valuable insights into a novel lncRNA-mediated regulatory mechanism in heart development and has implications for future theranostic applications targeting the Charme locus.
Long noncoding RNAs (lncRNAs) are emerging as critical regulators of heart physiology and disease, although the studies unveiling their modes of action are still limited to few examples. We recently identified pCharme, a chromatin-associated lncRNA whose functional knockout in mice results in defective myogenesis and morphological remodeling of the cardiac muscle. Here, we combined Cap-Analysis of Gene Expression (CAGE), single-cell (sc)RNA sequencing, and whole-mount in situ hybridization analyses to study pCharme cardiac expression. Since the early steps of cardiomyogenesis, we found the lncRNA being specifically restricted to cardiomyocytes, where it assists the formation of specific nuclear condensates containing MATR3, as well as important RNAs for cardiac development. In line with the functional significance of these activities, pCharme ablation in mice results in a delayed maturation of cardiomyocytes, which ultimately leads to morphological alterations of the ventricular myocardium. Since congenital anomalies in myocardium are clinically relevant in humans and predispose patients to major complications, the identification of novel genes controlling cardiac morphology becomes crucial. Our study offers unique insights into a novel lncRNA-mediated regulatory mechanism promoting cardiomyocyte maturation and bears relevance to Charme locus for future theranostic applications.
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