Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen
Language: 
English
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.

Author(s): 
Pedram Fatemi, Roya
Salah-Uddin, Sultan
Modarresi, Farzaneh
Khoury, Nathalie
Wahlestedt, Claes
Faghihi, Mohammad Ali
Item Type: 
Journal Article
Publication Title: 
Journal of Biomolecular Screening
Journal Abbreviation: 
J Biomol Screen
Publication Date: 
2015-10
Publication Year: 
2015
Pages: 
1132-1141
Volume: 
20
Issue: 
9
ISSN: 
1552-454X
DOI: 
10.1177/1087057115594187
Library Catalog: 
PubMed
Extra: 
PMID: 26173710 PMCID: PMC4576503

Turabian/Chicago Citation

Roya Pedram Fatemi, Sultan Salah-Uddin, Farzaneh Modarresi, Nathalie Khoury, Claes Wahlestedt and Mohammad Ali Faghihi. 2015-10. "Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen." Journal of Biomolecular Screening 20: 9: 1132-1141. 10.1177/1087057115594187.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1177/1087057115594187 | issn = 1552-454X | volume = 20 | pages = 1132-1141 | last = Pedram Fatemi | first = Roya | coauthors = Salah-Uddin, Sultan, Modarresi, Farzaneh, Khoury, Nathalie, Wahlestedt, Claes, Faghihi, Mohammad Ali | title = Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen | journal = Journal of Biomolecular Screening | date = 2015-10 | pmid = | pmc = }} </ref>