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 o
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.
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Metadaten
Author:Dorotée Julia Trembinski, Diewertje I. Bink, Kosta Theodorou, Janina Sommer, Ariane Fischer, Anke van Bergen, Chao-Chung Kuo, Ivan G. Costa, Christoph Schürmann, Matthias Leisegang, Ralf Peter Louis Brandes, Tijna Alekseeva, Boris Brill, Astrid Wietelmann, Christopher N. Johnson, Alexander Spring-Connell, Manuel Kaulich, Stanislas Werfel, Stefan Engelhardt, Marc Nikolaus Hirt, Kaja Yorgan, Thomas Eschenhagen, Luisa Kirchhof, Patrick Hofmann, Nicolas Christopher Jaé, Ilka Wittig, Nazha Hamdani, Corinne Bischof, Jaya Krishnan, Riekelt H. Houtkooper, Stefanie Dimmeler, Reinier Boon
URN:urn:nbn:de:hebis:30:3-535769
DOI:http://dx.doi.org/10.1038/s41467-020-15995-2
ISSN:2041-1723
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=32341350
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2020
Date of first Publication:2020/04/27
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/06/10
Tag:Apoptosis; Cardiology; Long non-coding RNAs
Volume:11
Issue:1, Art. 2039
Pagenumber:14
First Page:1
Last Page:14
Note:
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
Institutes:Medizin
Georg-Speyer-Haus
Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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