TY - JOUR T1 - HIF1α-AS1 is a DNA:DNA:RNA triplex-forming lncRNA interacting with the HUSH complex JF - bioRxiv DO - 10.1101/2021.10.11.463905 SP - 2021.10.11.463905 AU - Matthias S. Leisegang AU - Jasleen Kaur Bains AU - Sandra Seredinski AU - James A. Oo AU - Nina M. Krause AU - Chao-Chung Kuo AU - Stefan Günther AU - Nevcin Sentürk Cetin AU - Timothy Warwick AU - Can Cao AU - Frederike Boos AU - Judit Izquierdo Ponce AU - Rebecca Bednarz AU - Chanil Valasarajan AU - Dominik Fuhrmann AU - Jens Preussner AU - Mario Looso AU - Soni S. Pullamsetti AU - Marcel H. Schulz AU - Flávia Rezende AU - Ralf Gilsbach AU - Beatrice Pflüger-Müller AU - Ilka Wittig AU - Ingrid Grummt AU - Teodora Ribarska AU - Ivan G. Costa AU - Harald Schwalbe AU - Ralf P. Brandes Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/10/11/2021.10.11.463905.abstract N2 - DNA:DNA:RNA triplexes that are formed through Hoogsteen base-pairing 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 reduced 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 was down-regulated in pulmonary hypertension and loss-of-function approaches not only resulted in gene de-repression but also enhanced angiogenic capacity. As exemplified here with HIF1α-AS1, DNA:DNA:RNA triplex formation is a functionally important mechanism of trans-acting gene expression control.Competing Interest StatementThe authors have declared no competing interest. ER -