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645
Structure-function-guided drug development efforts to target lncRNAs
Hollie Watmuff1, Amy Crawford1, Bryan Eusse1
1Department of Chemistry, New York University, 31 Washington Place, New York, NY, USA.
Trends in Pharmacological Sciences
|July 31, 2025
Summary
Long noncoding RNAs (lncRNAs) are crucial regulators of cell processes and disease. Targeting their structures and protein interactions with novel therapeutics offers promising treatment strategies for lncRNA-mediated diseases.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Long noncoding RNAs (lncRNAs) are key regulators of cellular functions.
- Dysregulation of lncRNAs is implicated in various disease pathologies.
- Understanding lncRNA structure and interactions is vital for elucidating their roles.
Purpose of the Study:
- To review the role of lncRNAs in disease pathogenesis.
- To highlight structural features and protein interactions of lncRNAs.
- To explore therapeutic strategies targeting lncRNAs.
Main Methods:
- Review of recent advancements in structural probing techniques.
- Analysis of lncRNA-protein interactions.
- Case studies of well-characterized lncRNAs (MALAT1, HOTAIR, GAS5, NEAT1, XIST).
Main Results:
- Structural probing reveals critical motifs and RNA-protein interfaces in lncRNAs.
- Dysfunctional lncRNAs contribute significantly to disease progression.
- Specific lncRNAs like MALAT1 and HOTAIR are implicated in pathogenesis.
Conclusions:
- lncRNAs are critical players in disease development.
- Targeting lncRNA structural motifs and interfaces with therapeutics like small molecules and antisense oligonucleotides shows therapeutic potential.
- Further drug development efforts focusing on lncRNAs are warranted.
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