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) |
|---|---|
| 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 |
Fingerprint
Keywords
- AlphaScreen
- brain-derived neurotrophic factor (BDNF)
- brain-derived neurotrophic factor antisense (BDNFAS)
- Enhancer of zeste homolog 2 (EZH2)
- epigenetic enzyme
- hox transcript antisense RNA (HOTAIR)
- long noncoding RNA
- natural antisense transcript
- noncoding RNA
- RNA protein interaction
ASJC Scopus subject areas
- Analytical Chemistry
- Drug Discovery
- Pharmacology
- Biochemistry
- Molecular Medicine
- Biotechnology
Cite this
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 R; Faghihi, Mohammad A.
In: Journal of Biomolecular Screening, Vol. 20, No. 9, 22.10.2015, p. 1132-1141.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Screening for small-molecule modulators of long noncoding RNA-protein interactions using alphascreen
AU - Pedram Fatemi, Roya
AU - Salah-Uddin, Sultan
AU - Modarresi, Farzaneh
AU - Khoury, Nathalie
AU - Wahlestedt, Claes R
AU - Faghihi, Mohammad A
PY - 2015/10/22
Y1 - 2015/10/22
N2 - 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.
AB - 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.
KW - AlphaScreen
KW - brain-derived neurotrophic factor (BDNF)
KW - brain-derived neurotrophic factor antisense (BDNFAS)
KW - Enhancer of zeste homolog 2 (EZH2)
KW - epigenetic enzyme
KW - hox transcript antisense RNA (HOTAIR)
KW - long noncoding RNA
KW - natural antisense transcript
KW - noncoding RNA
KW - RNA protein interaction
UR - http://www.scopus.com/inward/record.url?scp=84942109693&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942109693&partnerID=8YFLogxK
U2 - 10.1177/1087057115594187
DO - 10.1177/1087057115594187
M3 - Article
C2 - 26173710
AN - SCOPUS:84942109693
VL - 20
SP - 1132
EP - 1141
JO - Journal of Biomolecular Screening
JF - Journal of Biomolecular Screening
SN - 1087-0571
IS - 9
ER -