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Rogala, Sandra; Ali, Tamer; Melissari, Maria-Theodora; Währisch, Sandra; Schuster, Peggy; Sarre, Alexandre; Emídio, Rebeca Cordellini; Boettger, Thomas; Rogg, Eva-Maria; Kaur, Jaskiran; Krishnan, Jaya; Dumbović, Gabrijela; Dimmeler, Stefanie; Ounzain, Samir; Pedrazzini, Thierry; Herrmann, Bernhard G; Grote, Phillip
Nature communications, 11/2023, Volume: 14, Issue: 1Journal Article
Abstract 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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