Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs

Samir Ounzain, Rudi Micheletti, Tal Beckmann, Blanche Schroen, Michael Alexanian, Iole Pezzuto, Stefania Crippa, Mohamed Nemir, Alexandre Sarre, Rory Johnson, Jerome Dauvillier, Frederic Burdet, Mark Ibberson, Roderic Guigo, Ioannis Xenarios, Stephane Heymans, Thierry Pedrazzini*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

183 Citations (Web of Science)

Abstract

Aim Heart disease is recognized as a consequence of dysregulation of cardiac gene regulatory networks. Previously, unappreciated components of such networks are the long non-coding RNAs (lncRNAs). Their roles in the heart remain to be elucidated. Thus, this study aimed to systematically characterize the cardiac long non-coding transcriptome post-myocardial infarction and to elucidate their potential roles in cardiac homoeostasis. Methods and results We annotated the mouse transcriptome after myocardial infarction via RNA sequencing and ab initio transcript reconstruction, and integrated genome-wide approaches to associate specific lncRNAs with developmental processes and physiological parameters. Expression of specific lncRNAs strongly correlated with defined parameters of cardiac dimensions and function. Using chromatin maps to infer lncRNA function, we identified many with potential roles in cardiogenesis and pathological remodelling. The vast majority was associated with active cardiac-specific enhancers. Importantly, oligonucleotide-mediated knockdown implicated novel lncRNAs in controlling expression of key regulatory proteins involved in cardiogenesis. Finally, we identified hundreds of human orthologues and demonstrate that particular candidates were differentially modulated in human heart disease. Conclusion These findings reveal hundreds of novel heart-specific lncRNAs with unique regulatory and functional characteristics relevant to maladaptive remodelling, cardiac function and possibly cardiac regeneration. This new class of molecules represents potential therapeutic targets for cardiac disease. Furthermore, their exquisite correlation with cardiac physiology renders them attractive candidate biomarkers to be used in the clinic.
Original languageEnglish
Pages (from-to)353-+
JournalEuropean Heart Journal
Volume36
Issue number6
DOIs
Publication statusPublished - 7 Feb 2015

Keywords

  • Myocardial infarction
  • Heart failure
  • Transcriptome
  • Long non-coding RNAs
  • Next generation sequencing

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