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Reversible Modulation of Aptamer-Ligand Binding in RNA Light-Up Aptamers Containing G-Quadruplex Using Chemical
Rashi Soni1, A Murali Krishna1, Shahaji H More1
1Department of Chemistry, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati, 517507, Andhra Pradesh, India.
Chembiochem : a European Journal of Chemical Biology
|November 10, 2022
Summary
Synthetic RNA G-quadruplexes can be reversibly switched between equilibrium and non-equilibrium states using chemical stimuli like silver ions and cysteine. This discovery enables novel designs for dynamic nucleic acid networks and RNA-based sensors.
Area of Science:
- Biochemistry and Molecular Biology
- Synthetic Biology
- Chemical Biology
Background:
- Natural biomolecules regulate equilibrium systems using stimuli to achieve non-equilibrium states for function.
- RNA aptamers with G-quadruplex structures are key components in various biological processes and synthetic systems.
Purpose of the Study:
- To demonstrate the reversible regulation of synthetic RNA G-quadruplex aptamer-ligand interactions between equilibrium and non-equilibrium states.
- To explore the use of simple chemical stimuli for controlling these dynamic nucleic acid interactions.
Main Methods:
- Design and synthesis of RNA aptamers featuring a G-quadruplex core structure.
- Application of chemical stimuli, specifically silver ions (Ag+) and cysteine, to induce transitions between equilibrium and non-equilibrium states.
- Monitoring and analysis of aptamer-ligand interaction dynamics under varying chemical conditions.
Main Results:
- Successfully demonstrated reversible switching of RNA G-quadruplex aptamer-ligand interactions from equilibrium to non-equilibrium states using Ag+ and cysteine.
- Reported for the first time that silver ions can disrupt RNA G-quadruplex structures.
- Validated the potential for precise control over aptamer-ligand binding in dynamic systems.
Conclusions:
- The developed method offers a novel strategy for designing dynamic nucleic acid networks requiring strict control over aptamer-ligand interactions.
- The findings provide new insights into the role of metal ions, particularly silver, in RNA folding, catalysis, and G-quadruplex stability.
- This work paves the way for advanced RNA-based sensors and regulators with tunable functionalities.

