Related Experiment Video

Updated: May 24, 2025

Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
05:37

Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes

Published on: April 4, 2025

312

Structural Insights into an Antiparallel Chair-Type G-Quadruplex From the Intron of NOP56 Oncogene

Zhenzhen Yan1, Axin He1,2, Liqi Wan1,2

  • 1Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 6, 2025
PubMed

Insights

Researchers discovered a unique G-quadruplex (G4) DNA structure in the NOP56 gene intron. This finding, along with the drug pyridostatin

Area of Science:

  • Structural biology
  • Molecular biology
  • Genetics

Background:

  • G-quadruplex (G4) structures are crucial in biological processes like gene regulation.
  • Nucleolar protein 56 (NOP56) is vital for ribosome biogenesis and is overexpressed in cancers, making it a therapeutic target.

Purpose of the Study:

  • To determine the high-resolution structure of a novel G4 formed by a DNA sequence from NOP56 intron 1.
  • To investigate the interaction of the G4 ligand pyridostatin (PDS) with this structure.
  • To assess the therapeutic potential of targeting this intronic G4 structure.

Main Methods:

  • Solution nuclear magnetic resonance (NMR) spectroscopy for high-resolution structure determination.
  • Melting temperature assays to evaluate ligand binding and stabilization.
  • Cancer cell line experiments to assess the effect of PDS on NOP56 mRNA levels.

Main Results:

  • The first reported antiparallel chair-type G4 structure from NOP56 intron 1 was elucidated.
  • The NOP56-G4 structure features two G-tetrads, a C·G·C·G tetrad, and a C∙C base pair.
  • Pyridostatin (PDS) binds to the terminal G-tetrad, increasing the G4 melting temperature by ~14 °C and reducing NOP56 mRNA in cancer cells.

Conclusions:

  • This study provides an unprecedented structural basis for a unique intronic G4 structure in NOP56.
  • Targeting intronic G4 structures offers a feasible strategy for gene regulation.
  • The findings open new avenues for G4 structure-based drug design and cancer therapeutics.
Keywords:
NOP56 intronDNA structureG‐quadruplexgene regulationsolution NMR

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