Journal Article

DKFZ-2019-02611

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Detection of RNA-DNA binding sites in long noncoding RNAs.

Kuo, C.-C. ; Hänzelmann, S. ; Sentürk Cetin, N.DKFZ* ; Frank, S. ; Zajzon, B. ; Derks, J.-P. ; Akhade, V. S. ; Ahuja, G. ; Kanduri, C. ; Grummt, I.DKFZ* ; Kurian, L. ; Costa, I. G.

2019
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/nar/gkz037

Abstract: Long non-coding RNAs (lncRNAs) can act as scaffolds that promote the interaction of proteins, RNA, and DNA. There is increasing evidence of sequence-specific interactions of lncRNAs with DNA via triple-helix (triplex) formation. This process allows lncRNAs to recruit protein complexes to specific genomic regions and regulate gene expression. Here we propose a computational method called Triplex Domain Finder (TDF) to detect triplexes and characterize DNA-binding domains and DNA targets statistically. Case studies showed that this approach can detect the known domains of lncRNAs Fendrr, HOTAIR and MEG3. Moreover, we validated a novel DNA-binding domain in MEG3 by a genome-wide sequencing method. We used TDF to perform a systematic analysis of the triplex-forming potential of lncRNAs relevant to human cardiac differentiation. We demonstrated that the lncRNA with the highest triplex-forming potential, GATA6-AS, forms triple helices in the promoter of genes relevant to cardiac development. Moreover, down-regulation of GATA6-AS impairs GATA6 expression and cardiac development. These data indicate the unique ability of our computational tool to identify novel triplex-forming lncRNAs and their target genes.

Keyword(s): HOTAIR long untranslated RNA, human ; RNA, Long Noncoding ; Transcription Factors ; DNA

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Contributing Institute(s):

1. Molekularbiologie der Zelle II (A030)

Research Program(s):

1. 311 - Signalling pathways, cell and tumor biology (POF3-311) (POF3-311)

Appears in the scientific report 2019

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