Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs
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- dc.contributor.author Ounzain, Samirca
- dc.contributor.author Micheletti, Rudica
- dc.contributor.author Beckmann, Talca
- dc.contributor.author Schroen, Blancheca
- dc.contributor.author Alexanian, Michaelca
- dc.contributor.author Pezzuto, Ioleca
- dc.contributor.author Crippa, Stefaniaca
- dc.contributor.author Nemir, Mohamedca
- dc.contributor.author Sarre, Alexandreca
- dc.contributor.author Johnson, Roryca
- dc.contributor.author Dauvillier, Jérômeca
- dc.contributor.author Burdet, Frédéricca
- dc.contributor.author Ibberson, Markca
- dc.contributor.author Guigó Serra, Rodericca
- dc.contributor.author Xenarios, Ioannisca
- dc.contributor.author Heymans, Stephaneca
- dc.contributor.author Pedrazzini, Thierryca
- dc.date.accessioned 2015-11-10T15:37:11Z
- dc.date.available 2015-11-10T15:37:11Z
- dc.date.issued 2015
- dc.description.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 postmyocardial 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,/nand 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.ca
- dc.format.mimetype application/pdfca
- dc.identifier.citation Ounzain S, Micheletti R, Beckmann T, Schroen B, Alexanian M, Pezzuto I et al. Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs. European Heart Journal. 2015; 36(6): 353-368. DOI 10.1093/eurheartj/ehu180ca
- dc.identifier.doi http://dx.doi.org/10.1093/eurheartj/ehu180
- dc.identifier.issn 0195-668X
- dc.identifier.uri http://hdl.handle.net/10230/25038
- dc.language.iso engca
- dc.publisher Oxford University Pressca
- dc.relation.ispartof European Heart Journal. 2015; 36(6): 353-368
- dc.rights © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License(http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by-nc/3.0/ca
- dc.subject.keyword Myocardial infarctionen
- dc.subject.keyword Heart failureen
- dc.subject.keyword Transcriptomeen
- dc.subject.keyword Long non-coding RNAsen
- dc.subject.keyword Next-generation sequencingen
- dc.subject.other Infart de miocardica
- dc.subject.other RNA no missatgersca
- dc.title Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAsca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca