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HIF1α-AS1 is a DNA:DNA:RNA triplex-forming lncRNA interacting with the HUSH complex

Author

Listed:
  • Matthias S. Leisegang

    (Goethe University
    Partner site RheinMain)

  • Jasleen Kaur Bains

    (Goethe University)

  • Sandra Seredinski

    (Goethe University
    Partner site RheinMain)

  • James A. Oo

    (Goethe University
    Partner site RheinMain)

  • Nina M. Krause

    (Goethe University)

  • Chao-Chung Kuo

    (Joint Research Center for Computational Biomedicine, RWTH Aachen Medical Faculty)

  • Stefan Günther

    (Max Planck Institute for Heart and Lung Research)

  • Nevcin Sentürk Cetin

    (German Cancer Research Center DKFZ-ZMBH)

  • Timothy Warwick

    (Goethe University
    Partner site RheinMain)

  • Can Cao

    (Goethe University)

  • Frederike Boos

    (Goethe University
    Partner site RheinMain)

  • Judit Izquierdo Ponce

    (Goethe University)

  • Shaza Haydar

    (Goethe University
    Partner site RheinMain)

  • Rebecca Bednarz

    (Goethe University)

  • Chanil Valasarajan

    (Max Planck Institute for Heart and Lung Research
    Justus Liebig University)

  • Dominik C. Fuhrmann

    (Goethe University)

  • Jens Preussner

    (Max Planck Institute for Heart and Lung Research)

  • Mario Looso

    (Max Planck Institute for Heart and Lung Research)

  • Soni S. Pullamsetti

    (Max Planck Institute for Heart and Lung Research
    Justus Liebig University)

  • Marcel H. Schulz

    (Partner site RheinMain
    Goethe University)

  • Hendrik R. A. Jonker

    (Goethe University)

  • Christian Richter

    (Goethe University)

  • Flávia Rezende

    (Goethe University
    Partner site RheinMain)

  • Ralf Gilsbach

    (Goethe University
    Partner site RheinMain)

  • Beatrice Pflüger-Müller

    (Goethe University
    Partner site RheinMain)

  • Ilka Wittig

    (Goethe University
    Partner site RheinMain
    Goethe University)

  • Ingrid Grummt

    (German Cancer Research Center DKFZ-ZMBH)

  • Teodora Ribarska

    (German Cancer Research Center DKFZ-ZMBH
    Oslo University Hospital)

  • Ivan G. Costa

    (Joint Research Center for Computational Biomedicine, RWTH Aachen Medical Faculty)

  • Harald Schwalbe

    (Goethe University)

  • Ralf P. Brandes

    (Goethe University
    Partner site RheinMain)

Abstract

DNA:DNA:RNA triplexes that are formed through Hoogsteen base-pairing of the RNA in the major groove of the DNA duplex have been observed in vitro, but the extent to which these interactions occur in cells and how they impact cellular functions remains elusive. Using a combination of bioinformatic techniques, RNA/DNA pulldown and biophysical studies, we set out to identify functionally important DNA:DNA:RNA triplex-forming long non-coding RNAs (lncRNA) in human endothelial cells. The lncRNA HIF1α-AS1 was retrieved as a top hit. Endogenous HIF1α-AS1 reduces the expression of numerous genes, including EPH Receptor A2 and Adrenomedullin through DNA:DNA:RNA triplex formation by acting as an adapter for the repressive human silencing hub complex (HUSH). Moreover, the oxygen-sensitive HIF1α-AS1 is down-regulated in pulmonary hypertension and loss-of-function approaches not only result in gene de-repression but also enhance angiogenic capacity. As exemplified here with HIF1α-AS1, DNA:DNA:RNA triplex formation is a functionally important mechanism of trans-acting gene expression control.

Suggested Citation

  • Matthias S. Leisegang & Jasleen Kaur Bains & Sandra Seredinski & James A. Oo & Nina M. Krause & Chao-Chung Kuo & Stefan Günther & Nevcin Sentürk Cetin & Timothy Warwick & Can Cao & Frederike Boos & Ju, 2022. "HIF1α-AS1 is a DNA:DNA:RNA triplex-forming lncRNA interacting with the HUSH complex," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34252-2
    DOI: 10.1038/s41467-022-34252-2
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    References listed on IDEAS

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    1. Tanmoy Mondal & Santhilal Subhash & Roshan Vaid & Stefan Enroth & Sireesha Uday & Björn Reinius & Sanhita Mitra & Arif Mohammed & Alva Rani James & Emily Hoberg & Aristidis Moustakas & Ulf Gyllensten , 2015. "MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA–DNA triplex structures," Nature Communications, Nature, vol. 6(1), pages 1-17, November.
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