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 remodelling 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.

The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart / Taliani, Valeria; Buonaiuto, Giulia; Desideri, Fabio; Setti, Adriano; Santini, Tiziana; Galfrè, Silvia; Schirone, Leonardo; Mariani, Davide; Frati, Giacomo; Valenti, Valentina; Sciarretta, Sebastiano; Perlas, Emerald; Nicoletti, Carmine; Musarò, Antonio; Ballarino, Monica. - In: ELIFE. - ISSN 2050-084X. - 12:(2023). [10.7554/eLife.81360]

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

Taliani, Valeria
Co-primo
Methodology
;
Buonaiuto, Giulia
Co-primo
Methodology
;
Setti, Adriano
Software
;
Santini, Tiziana
Methodology
;
Schirone, Leonardo
Membro del Collaboration Group
;
Frati, Giacomo
Membro del Collaboration Group
;
Sciarretta, Sebastiano
Membro del Collaboration Group
;
Nicoletti, Carmine
Membro del Collaboration Group
;
Musarò, Antonio
Membro del Collaboration Group
;
Ballarino, Monica
Ultimo
Funding Acquisition
2023

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 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. 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.
2023
chromosomes; developmental biology; gene expression; mouse
01 Pubblicazione su rivista::01a Articolo in rivista
The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart / Taliani, Valeria; Buonaiuto, Giulia; Desideri, Fabio; Setti, Adriano; Santini, Tiziana; Galfrè, Silvia; Schirone, Leonardo; Mariani, Davide; Frati, Giacomo; Valenti, Valentina; Sciarretta, Sebastiano; Perlas, Emerald; Nicoletti, Carmine; Musarò, Antonio; Ballarino, Monica. - In: ELIFE. - ISSN 2050-084X. - 12:(2023). [10.7554/eLife.81360]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1674499
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