The lncRNASweetheartregulates compensatory cardiac hypertrophy after myocardial injury

Abstract

ABSTRACTAfter 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 now recognized for taking part in fine-tuning such gene programs. We identified and characterized the cardiomyocyte specific lncRNASweetheart RNA(Swhtr), an approximately 10 kb long transcript divergently expressed from the cardiac core transcription factor coding geneNkx2-5. We show thatSwhtris dispensable for normal heart development and function, but becomes essential for the tissue adaptation process after myocardial infarction. Re-expressingSwhtrfrom an exogenous locus rescues theSwhtr nullphenotype. Genes depending onSwhtrafter cardiac stress are significantly occupied, and therefore most likely regulated by NKX2-5. Our results indicate a synergistic role forSwhtrand the developmentally essential transcription factor NKX2-5 in tissue adaptation after myocardial injury.