Reversible Control of RNA Splicing by Photoswitchable Small Molecules

Area of Science:

• Molecular Biology
• RNA Biology
• Photochemistry

Background:

• RNA dynamics are crucial for function and structure, but spatiotemporal control remains challenging.
• Current methods for regulating RNA processes lack precise temporal resolution.

Purpose of the Study:

• To pioneer a reversible, light-inducible system for controlling RNA splicing in primary cells.
• To demonstrate the potential of synthetic photoswitches in modulating RNA splicing with spatiotemporal precision.

Main Methods:

• Utilized synthetic photoswitches and small molecules for conditional RNA splicing regulation.
• Employed Nuclear Magnetic Resonance (NMR) spectroscopy, theoretical calculations, photochemical characterization, and fluorescence polarization assays.
• Validated the approach using living cell-based assays.

Main Results:

• Demonstrated light-dependent control over exon inclusion in RNA splicing.
• Observed a significant increase in target functional protein levels upon light activation.
• Confirmed the reversible nature of the photoswitch-mediated splicing modulation.

Conclusions:

• Successfully established a photopharmacology-based method for real-time RNA splicing regulation.
• The developed small molecule offers conditional, light-triggered control at both mRNA and protein levels.
• This approach expands the optochemical toolkit and holds promise for RNA-based therapeutic innovations.