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

Humans RNA, Long Noncoding / genetics Endothelial Cells / metabolism DNA / genetics Base Pairing Oligonucleotides Gene Expression Regulation, Neoplastic

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
02 11 2022

Historique:

received: 29 09 2021

accepted: 19 10 2022

entrez: 3 11 2022

pubmed: 4 11 2022

medline: 5 11 2022

Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-022-34252-2 PMID: 36323673 PMC: PMC9630315

pubmed: 36323673

doi: 10.1038/s41467-022-34252-2

pii: 10.1038/s41467-022-34252-2

pmc: PMC9630315

doi:

Substances chimiques

RNA, Long Noncoding 0

DNA 9007-49-2

Oligonucleotides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

6563

Informations de copyright

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