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

Author

Listed:
  • D. Julia Trembinski

    (Goethe University Frankfurt am Main
    German Center for Cardiovascular Research (DZHK))

  • Diewertje I. Bink

    (VU University Medical Center)

  • Kosta Theodorou

    (Goethe University Frankfurt am Main
    German Center for Cardiovascular Research (DZHK))

  • Janina Sommer

    (Goethe University Frankfurt am Main)

  • Ariane Fischer

    (Goethe University Frankfurt am Main)

  • Anke Bergen

    (VU University Medical Center)

  • Chao-Chung Kuo

    (RWTH Aachen University)

  • Ivan G. Costa

    (RWTH Aachen University)

  • Christoph Schürmann

    (Goethe University Frankfurt am Main)

  • Matthias S. Leisegang

    (German Center for Cardiovascular Research (DZHK)
    Goethe University Frankfurt am Main)

  • Ralf P. Brandes

    (German Center for Cardiovascular Research (DZHK)
    Goethe University Frankfurt am Main)

  • Tijna Alekseeva

    (Georg Speyer Haus, Institute for Tumor Biology and Experimental Therapy)

  • Boris Brill

    (Georg Speyer Haus, Institute for Tumor Biology and Experimental Therapy)

  • Astrid Wietelmann

    (Max-Planck-Institute for Heart and Lung Research)

  • Christopher N. Johnson

    (Vanderbilt University Medical Center)

  • Alexander Spring-Connell

    (Georgia State University)

  • Manuel Kaulich

    (Goethe University)

  • Stanislas Werfel

    (German Center for Cardiovascular Research (DZHK)
    Technical University Munich
    Technical University of Munich, School of Medicine, Klinikum rechts der Isar)

  • Stefan Engelhardt

    (German Center for Cardiovascular Research (DZHK)
    Technical University Munich)

  • Marc N. Hirt

    (German Center for Cardiovascular Research (DZHK)
    University Medical Center Hamburg-Eppendorf)

  • Kaja Yorgan

    (German Center for Cardiovascular Research (DZHK)
    University Medical Center Hamburg-Eppendorf)

  • Thomas Eschenhagen

    (German Center for Cardiovascular Research (DZHK)
    University Medical Center Hamburg-Eppendorf)

  • Luisa Kirchhof

    (Goethe University Frankfurt am Main)

  • Patrick Hofmann

    (Goethe University Frankfurt am Main
    German Center for Cardiovascular Research (DZHK))

  • Nicolas Jaé

    (Goethe University Frankfurt am Main)

  • Ilka Wittig

    (German Center for Cardiovascular Research (DZHK)
    Goethe University Frankfurt am Main)

  • Nazha Hamdani

    (VU University Medical Center
    Ruhr University Bochum)

  • Corinne Bischof

    (Goethe University Frankfurt am Main)

  • Jaya Krishnan

    (Goethe University Frankfurt am Main)

  • Riekelt H. Houtkooper

    (Academic Medical Center)

  • Stefanie Dimmeler

    (Goethe University Frankfurt am Main
    German Center for Cardiovascular Research (DZHK))

  • Reinier A. Boon

    (Goethe University Frankfurt am Main
    German Center for Cardiovascular Research (DZHK)
    VU University Medical Center)

Abstract

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.

Suggested Citation

  • D. Julia Trembinski & Diewertje I. Bink & Kosta Theodorou & Janina Sommer & Ariane Fischer & Anke Bergen & Chao-Chung Kuo & Ivan G. Costa & Christoph Schürmann & Matthias S. Leisegang & Ralf P. Brande, 2020. "Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15995-2
    DOI: 10.1038/s41467-020-15995-2
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