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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.

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|July 31, 2025
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Summary
This summary is machine-generated.

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.

Keywords:
GAS5HOTAIRMALAT1NEAT1RNA structureRNA therapeuticsXISTantisense oligoslong noncoding RNAsmall molecules

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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.