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Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen

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 the...

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Autores principales: Pedram Fatemi, Roya, Salah-Uddin, Sultan, Modarresi, Farzaneh, Khoury, Nathalie, Wahlestedt, Claes, Faghihi, Mohammad Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576503/
https://www.ncbi.nlm.nih.gov/pubmed/26173710
http://dx.doi.org/10.1177/1087057115594187
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author Pedram Fatemi, Roya
Salah-Uddin, Sultan
Modarresi, Farzaneh
Khoury, Nathalie
Wahlestedt, Claes
Faghihi, Mohammad Ali
author_facet Pedram Fatemi, Roya
Salah-Uddin, Sultan
Modarresi, Farzaneh
Khoury, Nathalie
Wahlestedt, Claes
Faghihi, Mohammad Ali
author_sort Pedram Fatemi, Roya
collection PubMed
description 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.
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spelling pubmed-45765032015-09-30 Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen Pedram Fatemi, Roya Salah-Uddin, Sultan Modarresi, Farzaneh Khoury, Nathalie Wahlestedt, Claes Faghihi, Mohammad Ali J Biomol Screen Original Research 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. SAGE Publications 2015-10 /pmc/articles/PMC4576503/ /pubmed/26173710 http://dx.doi.org/10.1177/1087057115594187 Text en © 2015 Society for Laboratory Automation and Screening http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (http://www.uk.sagepub.com/aboutus/openaccess.htm).
spellingShingle Original Research
Pedram Fatemi, Roya
Salah-Uddin, Sultan
Modarresi, Farzaneh
Khoury, Nathalie
Wahlestedt, Claes
Faghihi, Mohammad Ali
Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen
title Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen
title_full Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen
title_fullStr Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen
title_full_unstemmed Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen
title_short Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen
title_sort screening for small-molecule modulators of long noncoding rna-protein interactions using alphascreen
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576503/
https://www.ncbi.nlm.nih.gov/pubmed/26173710
http://dx.doi.org/10.1177/1087057115594187
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