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Designing Reversible Photoswitching Azobenzene-Modified Nucleotide for Controlling Biological Function.

Juncheng Li1,2, Jinxi Du1,2, Weiwei He3,4

  • 1The RNA Institute, University at Albany, State University of New York, Albany, New York 12222, United States.

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|June 13, 2025
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This summary is machine-generated.

Researchers developed a photoswitchable RNA molecule that can be controlled with light. This innovation allows for reversible optical control of RNA structures and functions, paving the way for new gene regulation and therapeutic strategies.

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Area of Science:

  • Chemical Biology
  • Molecular Biology
  • RNA Therapeutics

Background:

  • RNA molecules are crucial for cellular functions and disease processes.
  • Controlling RNA structure and function with light offers a powerful method for biological regulation and therapeutic development.

Purpose of the Study:

  • To design and synthesize azobenzene-modified cytidine phosphoramidite for creating photoswitchable oligoribonucleotides.
  • To investigate the reversible photoisomerization and impact of this modification on RNA structure and function.
  • To demonstrate light-controlled regulation of the reverse transcription process using modified RNA.

Main Methods:

  • Synthesis of azobenzene-modified cytidine phosphoramidite and oligoribonucleotides.
  • Validation of photoisomerization using UV melting experiments and all-atom molecular dynamics (MD) simulations.
  • Demonstration of light-induced switching of the reverse transcription (RT) process with various RT enzymes.

Main Results:

  • Successful synthesis and validation of reversible photoisomerization in modified ribonucleosides and oligoribonucleotides.
  • MD simulations and UV melting experiments revealed the impact of the cytidine modification.
  • Demonstrated optical control over the RT process, including HIV reverse transcriptase-mediated RT, elucidated by MD simulation.

Conclusions:

  • A novel chemical biology toolset for reversible optical control of RNA structures and functions has been developed.
  • This technology holds promise for advancing gene regulation strategies and the development of novel RNA-based therapeutics.