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Detection of RNA-DNA binding sites in long noncoding RNAs.

Journal article
Authors Chao-Chung Kuo
Sonja Hänzelmann
Nevcin Sentürk Cetin
Stefan Frank
Barna Zajzon
Jens-Peter Derks
Vijay Suresh Akhade
Gaurav Ahuja
Chandrasekhar Kanduri
Ingrid Grummt
Leo Kurian
Ivan G Costa
Published in Nucleic acids research
Volume 47
Issue 6
ISSN 1362-4962
Publication year 2019
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Language en
Links dx.doi.org/10.1093/nar/gkz037
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Biochemistry and Molecular Biology

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.

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