Sandra Rogala, Tamer Ali, Maria-Theodora Melissari, Sandra Währisch, Peggy Schuster, Alexandre Sarre, Rebeca Cordellini Emídio, Thomas Böttger, Eva-Maria Pia Rogg, Jaskiran Kaur, Jaya Krishnan, Gabrijela Dumbović, Stefanie Dimmeler, Samir Ounzain, Thierry Pedrazzini, Bernhard Herrmann, Phillip Grote
- 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.
