TY  - JOUR
A1  - Trembinski, Dorotée Julia
A1  - Bink, Diewertje I.
A1  - Theodorou, Kosta
A1  - Sommer, Janina
A1  - Fischer, Ariane
A1  - Bergen, Anke van
A1  - Kuo, Chao-Chung
A1  - Costa, Ivan G.
A1  - Schürmann, Christoph
A1  - Leisegang, Matthias
A1  - Brandes, Ralf
A1  - Alekseeva, Tijna
A1  - Brill, Boris
A1  - Wietelmann, Astrid
A1  - Johnson, Christopher N.
A1  - Spring-Connell, Alexander
A1  - Kaulich, Manuel
A1  - Werfel, Stanislas
A1  - Engelhardt, Stefan
A1  - Hirt, Marc Nikolaus
A1  - Yorgan, Kaja
A1  - Eschenhagen, Thomas
A1  - Kirchhof, Luisa
A1  - Hofmann, Patrick
A1  - Jaé, Nicolas Christopher
A1  - Wittig, Ilka
A1  - Hamdani, Nazha
A1  - Bischof, Corinne
A1  - Krishnan, Jaya
A1  - Houtkooper, Riekelt H.
A1  - Dimmeler, Stefanie
A1  - Boon, Reinier
T1  - Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction
T2  - Nature Communications
N2  - 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.
KW  - Apoptosis
KW  - Cardiology
KW  - Long non-coding RNAs
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53576
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-535769
SN  - 2041-1723
N1  - 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/.
VL  - 11
IS  - 1, Art. 2039
SP  - 1
EP  - 14
PB  - Nature Publishing Group UK
CY  - [London]
ER  -