Targeting RNA in mammalian systems with small molecules

Area of Science:

• Molecular Biology
• RNA Therapeutics
• Chemical Biology

Background:

• The central dogma of molecular biology is being challenged by the discovery of RNA's diverse regulatory functions beyond protein synthesis.
• Dysregulation of RNA-mediated cellular processes contributes to various diseases, highlighting RNA as a potential therapeutic target.
• Advances in genomics have revealed novel RNA classes in mammals, intensifying research into their roles in disease.

Purpose of the Study:

• To review the growing field of small molecule-RNA interactions for therapeutic intervention.
• To highlight the potential of targeting RNA structural domains and their interactions.
• To encourage further exploration of RNA-based therapeutics, particularly for emerging RNA classes.

Main Methods:

• Review of existing literature on small molecule-RNA interactions and their therapeutic applications.
• Analysis of successful examples targeting expanded repeats, microRNAs, G-quadruplexes, and splice sites.
• Discussion of fundamental principles of small molecule-RNA recognition and methodological advancements.

Main Results:

• Bioactive small molecules have been identified that modulate disease phenotypes by interacting with specific RNA structures.
• These molecules target diverse RNA elements, including expanded repeats, microRNAs, G-quadruplexes, and splice sites.
• Successful examples exist in treating neurological disorders, cancers, and other diseases.

Conclusions:

• Small molecules represent a promising strategy for modulating RNA function and treating diseases.
• Targeting RNA structures offers a powerful approach for developing novel therapeutics.
• Continued research into small molecule-RNA recognition and new RNA classes will unlock further therapeutic potential.