Exploring Small-Molecule Modulators of Precursor miRNA Processing Associated With Glycolysis.

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• MicroRNAs (miRNAs) are small noncoding RNAs crucial for gene expression regulation.
• They influence numerous physiological processes, with human miRNAs potentially regulating 60% of protein-coding genes.
• Targeting miRNA biogenesis with small molecules offers a route to modulate cellular functions.

Purpose of the Study:

• To identify small-molecule binders targeting precursor microRNAs (pre-miRNAs).
• To evaluate the impact of identified compounds on Dicer-mediated pre-miRNA processing.

Main Methods:

• High-throughput screening of 2320 known compounds using a fluorescent indicator displacement (FID) assay.
• Two sequential FID screenings to identify candidate compounds interacting with pre-miRNAs.
• Surface plasmon resonance (SPR) analysis to confirm compound binding to pre-miRNAs.
• Assessment of compound effects on Dicer enzyme activity in pre-miRNA processing.

Main Results:

• 34 candidate compounds were identified through sequential FID screenings.
• SPR analysis confirmed the binding of candidate compounds to target pre-miRNAs.
• Several compounds demonstrated inhibitory effects on Dicer-mediated pre-miRNA processing.

Conclusions:

• This study successfully identified small molecules capable of binding to pre-miRNAs.
• Several identified compounds inhibit the Dicer-mediated processing of pre-miRNAs.
• These findings provide potential therapeutic leads for modulating miRNA biogenesis and function.