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

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

The following data sets were generated
The following previously published data sets were used
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Article and author information

Author details

  1. Valeria Taliani

    Department of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6449-735X
  2. Giulia Buonaiuto

    Department of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4099-2433
  3. Fabio Desideri

    Center for Life Nano- and Neuro-Science, Istituto Italiano di Tecnologia (IIT), Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  4. Adriano Setti

    Department of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Tiziana Santini

    Department of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  6. Silvia Galfrè

    Center for Life Nano- and Neuro-Science, Istituto Italiano di Tecnologia (IIT), Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  7. Leonardo Schirone

    Department of Medical Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
    Competing interests
    The authors declare that no competing interests exist.
  8. Davide Mariani

    Center for Human Technologies, Istituto Italiano di Tecnologia (IIT), Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0903-5632
  9. Giacomo Frati

    Department of Medical Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
    Competing interests
    The authors declare that no competing interests exist.
  10. Valentina Valenti

    Department of Medical Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
    Competing interests
    The authors declare that no competing interests exist.
  11. Sebastiano Sciarretta

    Department of Medical Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
    Competing interests
    The authors declare that no competing interests exist.
  12. Emerald Perlas

    Epigenetics and Neurobiology Unit, EMBL-Rome, Monterotondo, Italy
    Competing interests
    The authors declare that no competing interests exist.
  13. Carmine Nicoletti

    DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5896-2040
  14. Antonio Musarò

    DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  15. Monica Ballarino

    Department of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy
    For correspondence
    monica.ballarino@uniroma1.it
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8595-7105

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

  1. 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

  1. Received: June 24, 2022
  2. Preprint posted: July 5, 2022 (view preprint)
  3. Accepted: March 3, 2023
  4. Accepted Manuscript published: March 6, 2023 (version 1)
  5. 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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  1. Valeria Taliani
  2. Giulia Buonaiuto
  3. Fabio Desideri
  4. Adriano Setti
  5. Tiziana Santini
  6. Silvia Galfrè
  7. Leonardo Schirone
  8. Davide Mariani
  9. Giacomo Frati
  10. Valentina Valenti
  11. Sebastiano Sciarretta
  12. Emerald Perlas
  13. Carmine Nicoletti
  14. Antonio Musarò
  15. Monica Ballarino
(2023)
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

Share this article

https://doi.org/10.7554/eLife.81360

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