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Published on: July 21, 2021
Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen.
Roya Pedram Fatemi1, Sultan Salah-Uddin2, Farzaneh Modarresi2
1Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA Department of Psychiatry and Behavioral Sciences and Center for Therapeutic Innovation, University of Miami Miller School of Medicine, Miami, FL, USA.
Researchers developed a high-throughput screening tool to identify small molecules that modulate long non-coding RNA (lncRNA)-protein interactions. They found ellipticine, a compound that up-regulates brain-derived neurotrophic factor (BDNF) transcription by affecting lncRNA-protein interactions.
Area of Science:
- Molecular Biology
- Epigenetics
- Drug Discovery
Background:
- Long non-coding RNAs (lncRNAs) are crucial regulators of cellular processes, often interacting with epigenetic enzymes.
- The precise functions and interaction mechanisms of most lncRNAs remain largely uncharacterized.
- Targeting lncRNA-protein interactions offers a potential therapeutic strategy for various human disorders.
Purpose of the Study:
- To develop a high-throughput screening (HTS) assay for identifying modulators of lncRNA-protein interactions.
- To screen a phytochemical library for small molecules that inhibit or modulate the interaction between specific lncRNAs and the EZH2 enzyme.
- To explore the therapeutic potential of targeting lncRNA-protein interactions.
Main Methods:
- Development of an AlphaScreen-based assay to detect lncRNA-protein interactions.
- High-throughput screening of a phytochemical library against interactions involving brain-derived neurotrophic factor antisense (BDNF-AS) and Hox transcript antisense RNA (HOTAIR) with Enhancer of zeste homolog 2 (EZH2).
- Validation of identified compounds for their effects on gene expression.
Main Results:
- Successful implementation of an HTS assay for lncRNA-protein interactions.
- Identification of ellipticine as a compound that up-regulates brain-derived neurotrophic factor (BDNF) transcription.
- Demonstration of ellipticine's ability to modulate lncRNA-protein interactions.
Conclusions:
- High-throughput screening is a feasible approach for discovering modulators of lncRNA-protein interactions.
- Ellipticine represents a potential therapeutic lead for targeting BDNF transcription via lncRNA modulation.
- This work provides a foundation for developing small-molecule therapies targeting dysregulated lncRNAs in human diseases.
