The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart
- Sapienza University of Rome, Italy
- Istituto Italiano di Tecnologia (IIT), Italy
- EMBL-Rome, Italy
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.
Data availability
Sequencing data presented in this study have been deposited in the NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) under the accession codes: GSE200878 and GSE200877.All data analysed from previously published datasets have been cited in the manuscript
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Effect of Charme lncRNA knockout (KO) in cardiac development [RNA-seq]NCBI Gene Expression Omnibus, GSE200878.
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Identification of MATR3 RNA-interactors in WT and Charme KO condtion during cardiac development [CLIP-seq]NCBI Gene Expression Omnibus, GSE200877.
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FANTOM5 CAGE profiles of human and mouse samplesZenbu Genome Browser.
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Single cell RNA-seq data for control and epicardial-specific Prmt1-deletion hearts at E12.5NCBI Gene Expression Omnibus, GSE144271.
Article and author information
Author details
Funding
Sapienza Università di Roma (RM11916B7A39DCE5)
- Monica Ballarino
Sapienza Università di Roma (RM12117A5DE7A45B)
- Monica Ballarino
Regione Lazio (2020-T0002E0001)
- Monica Ballarino
Ministero dell'Istruzione, dell'Università e della Ricerca (CN3221842F1B2436 CN3_Spoke 3)
- Monica Ballarino
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Lucile Miquerol, Aix-Marseille University, IBDM, France
Ethics
Animal experimentation: All mice used in this work were C57BL6/J mice and all procedures involving laboratory animals were performed according to the institutional and national guidelines and legislations of Italy and according to the guidelines of Good Laboratory Practice (GLP). All experiments were approved by the Institutional Animal Use and Care Committee and carried out in accordance with the law (Protocol number 82945.56). MB has successfully completed the Module1 as co-coordinated by the Administration of Animal Facilities in the premises of EMBL. The EMBL course meets the requirements of European legislation on basic training of researchers.
Version history
- Received: June 24, 2022
- Preprint posted: July 5, 2022 (view preprint)
- Accepted: March 3, 2023
- Accepted Manuscript published: March 6, 2023 (version 1)
- Version of Record published: March 17, 2023 (version 2)
Copyright
© 2023, Taliani et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart
eLife 12:e81360.
https://doi.org/10.7554/eLife.81360
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