The lncRNA Sweetheart regulates compensatory cardiac hypertrophy after myocardial injury in murine males

  • After myocardial infarction in the adult heart the remaining, non-infarcted tissue adapts to compensate the loss of functional tissue. This adaptation requires changes in gene expression networks, which are mostly controlled by transcription regulating proteins. Long non-coding transcripts (lncRNAs) are taking part in fine-tuning such gene programs. We describe and characterize the cardiomyocyte specific lncRNA Sweetheart RNA (Swhtr), an approximately 10 kb long transcript divergently expressed from the cardiac core transcription factor coding gene Nkx2-5. We show that Swhtr is dispensable for normal heart development and function but becomes essential for the tissue adaptation process after myocardial infarction in murine males. Re-expressing Swhtr from an exogenous locus rescues the Swhtr null phenotype. Genes that depend on Swhtr after cardiac stress are significantly occupied and therefore most likely regulated by NKX2-5. The Swhtr transcript interacts with NKX2-5 and disperses upon hypoxic stress in cardiomyocytes, indicating an auxiliary role of Swhtr for NKX2-5 function in tissue adaptation after myocardial injury.

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Author:Sandra RogalaGND, Tamer AliORCiD, Maria-Theodora MelissariORCiD, Sandra Währisch, Peggy Schuster, Alexandre Sarre, Rebeca Cordellini Emídio, Thomas BöttgerORCiD, Eva-Maria Pia RoggGND, Jaskiran KaurGND, Jaya KrishnanORCiD, Gabrijela DumbovićORCiD, Stefanie DimmelerORCiDGND, Samir OunzainORCiD, Thierry PedrazziniORCiD, Bernhard HerrmannORCiDGND, Phillip GroteORCiD
URN:urn:nbn:de:hebis:30:3-855653
DOI:https://doi.org/10.1038/s41467-023-42760-y
ISSN:2041-1723
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2023/11/02
Date of first Publication:2023/11/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/05/24
Volume:14
Issue:article number: 7024
Article Number:7024
Page Number:14
Institutes:Medizin
Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International