Harnessing Molecular Recognition for Small-Molecule-Mediated Reversible Photochemical Control Over mRNA Translation

Area of Science:

• Chemical Biology
• Molecular Biology
• RNA Therapeutics

Background:

• Chemical probes offer precise control over biological systems.
• RNA aptamers are key targets for molecular recognition.
• Photochemical control provides spatiotemporal regulation.

Purpose of the Study:

• To develop a small molecule-controlled photocrosslinking system for RNA aptamers.
• To demonstrate light-inducible translation activation of mRNA constructs.
• To investigate the selectivity and mechanism of photocrosslinking.

Main Methods:

• Synthesis of a small molecule ligand for PreQ1 RNA aptamers.
• Development of caged mRNA constructs with PreQ1 aptamers.
• Photocrosslinking studies using 302 nm light.
• In vitro and in cell-based translation assays.

Main Results:

• Selective, traceless, and reversible photocrosslinking of PreQ1 aptamers by the small molecule ligand.
• Photocaged mRNA constructs showed repressed translation.
• 302 nm light irradiation led to photocage cleavage and translation restoration.
• Demonstrated precise, photochemical control over mRNA translation in cells.

Conclusions:

• Aptamer-based molecular recognition of small molecules can be coupled with photocrosslinking.
• This system enables precise, light-activated control of mRNA translation.
• This approach holds potential for developing novel RNA-based therapeutics and research tools.