Abstract
Long non-protein coding RNAs (lncRNAs) are an important class of molecules that help orchestrate key cellular events. Although their functional roles in cells are not well understood, thousands of lncRNAs and a number of possible mechanisms by which they act have been reported. LncRNAs can exert their regulatory function in cells by interacting with epigenetic enzymes. In this study, we developed a tool to study lncRNA-protein interactions for high-throughput screening of small-molecule modulators using AlphaScreen technology. We tested the interaction of two lncRNAs: brain-derived neurotrophic factor antisense (BDNF-AS) and Hox transcript antisense RNA (HOTAIR), with Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase against a phytochemical library, to look for small-molecule inhibitors that can alter the expression of downstream target genes. We identified ellipticine, a compound that up-regulates BDNF transcription. Our study shows the feasibility of using high-throughput screening to identify modulators of lncRNA-protein interactions and paves the road for targeting lncRNAs that are dysregulated in human disorders using small-molecule therapies.
Original language | English (US) |
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Pages (from-to) | 1132-1141 |
Number of pages | 10 |
Journal | Journal of Biomolecular Screening |
Volume | 20 |
Issue number | 9 |
DOIs | |
State | Published - Oct 22 2015 |
Keywords
- AlphaScreen
- Enhancer of zeste homolog 2 (EZH2)
- RNA protein interaction
- brain-derived neurotrophic factor (BDNF)
- brain-derived neurotrophic factor antisense (BDNFAS)
- epigenetic enzyme
- hox transcript antisense RNA (HOTAIR)
- long noncoding RNA
- natural antisense transcript
- noncoding RNA
ASJC Scopus subject areas
- Analytical Chemistry
- Biotechnology
- Biochemistry
- Molecular Medicine
- Pharmacology
- Drug Discovery