The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the...

Area of Science:

• Molecular Biology
• Genetics
• Cardiovascular Research

Background:

• Long noncoding RNAs (lncRNAs) play roles in heart function and disease.
• Few lncRNAs' functions in the heart are understood.
• pCharme, a chromatin-associated lncRNA, impacts cardiac muscle development.

Purpose of the Study:

• To investigate the cardiac expression and function of the lncRNA pCharme.
• To elucidate the molecular mechanisms by which pCharme regulates cardiomyocyte maturation.
• To understand the implications of pCharme in cardiac morphology and development.

Main Methods:

• Cap-Analysis of Gene Expression (CAGE) for gene expression profiling.
• Single-cell (sc)RNA sequencing to analyze cell-specific expression.
• Whole-mount in situ hybridization for spatial expression analysis.
• Functional knockout studies in mice to assess pCharme's role.

Main Results:

• pCharme is specifically expressed in cardiomyocytes during early development.
• pCharme facilitates the formation of nuclear condensates involving MATR3 and cardiac RNAs.
• Ablation of pCharme leads to delayed cardiomyocyte maturation and ventricular myocardium alterations.
• pCharme is crucial for proper cardiac muscle development and morphology.

Conclusions:

• pCharme is a novel regulator of cardiomyocyte maturation and cardiac development.
• The pCharme-MATR3 nuclear condensates are important for cardiac gene regulation.
• Understanding pCharme's role offers insights into congenital heart anomalies.
• The Charme locus holds potential for future theranostic applications in cardiac disease.