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Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction

  • Long non-coding RNAs (lncRNAs) contribute to cardiac (patho)physiology. Aging is the major risk factor for cardiovascular disease with cardiomyocyte apoptosis as one underlying cause. Here, we report the identification of the aging-regulated lncRNA Sarrah (ENSMUST00000140003) that is anti-apoptotic in cardiomyocytes. Importantly, loss of SARRAH (OXCT1-AS1) in human engineered heart tissue results in impaired contractile force development. SARRAH directly binds to the promoters of genes downregulated after SARRAH silencing via RNA-DNA triple helix formation and cardiomyocytes lacking the triple helix forming domain of Sarrah show an increase in apoptosis. One of the direct SARRAH targets is NRF2, and restoration of NRF2 levels after SARRAH silencing partially rescues the reduction in cell viability. Overexpression of Sarrah in mice shows better recovery of cardiac contractile function after AMI compared to control mice. In summary, we identified the anti-apoptotic evolutionary conserved lncRNA Sarrah, which is downregulated by aging, as a regulator of cardiomyocyte survival.
Metadaten
Verfasserangaben:Dorotée Julia Trembinski, Diewertje I. BinkORCiD, Kosta Theodorou, Janina Sommer, Ariane Fischer, Anke van BergenORCiD, Chao-Chung KuoORCiDGND, Ivan G. CostaORCiDGND, Christoph SchürmannORCiDGND, Matthias LeisegangORCiDGND, Ralf BrandesORCiDGND, Tijna Alekseeva, Boris Brill, Astrid Wietelmann, Christopher N. Johnson, Alexander Spring-Connell, Manuel KaulichORCiD, Stanislas Werfel, Stefan EngelhardtORCiD, Marc Nikolaus Hirt, Kaja Yorgan, Thomas EschenhagenORCiDGND, Luisa KirchhofORCiDGND, Patrick Hofmann, Nicolas Christopher JaéGND, Ilka WittigORCiD, Nazha Hamdani, Corinne Bischof, Jaya KrishnanORCiD, Riekelt H. HoutkooperORCiD, Stefanie DimmelerORCiDGND, Reinier BoonORCiDGND
URN:urn:nbn:de:hebis:30:3-535769
DOI:https://doi.org/10.1038/s41467-020-15995-2
ISSN:2041-1723
Pubmed-Id:https://pubmed.ncbi.nlm.nih.gov/32341350
Titel des übergeordneten Werkes (Englisch):Nature Communications
Verlag:Nature Publishing Group UK
Verlagsort:[London]
Dokumentart:Wissenschaftlicher Artikel
Sprache:Englisch
Jahr der Fertigstellung:2020
Datum der Erstveröffentlichung:27.04.2020
Veröffentlichende Institution:Universitätsbibliothek Johann Christian Senckenberg
Datum der Freischaltung:10.06.2020
Freies Schlagwort / Tag:Apoptosis; Cardiology; Long non-coding RNAs
Jahrgang:11
Ausgabe / Heft:1, Art. 2039
Seitenzahl:14
Erste Seite:1
Letzte Seite:14
Bemerkung:
Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
HeBIS-PPN:467143315
Institute:Medizin / Medizin
Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe
DDC-Klassifikation:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Lizenz (Deutsch):License LogoCreative Commons - Namensnennung 4.0

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