Oleic Acid Induces MiR-7 Processing through Remodeling of Pri-MiR-7/Protein Complex

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• MicroRNAs (miRs) are critical regulators of cellular functions, with their biogenesis controlled at multiple levels.
• RNA-binding proteins (RBPs) interact with primary miRs (pri-miRs) and precursor miRs (pre-miRs) to modulate their post-transcriptional processing.
• The interaction of Hu antigen R (HuR) and Musashi homolog2 (MSI2) with pri-miR-7 regulates brain-enriched miR-7 levels.

Purpose of the Study:

• To investigate the effect of oleic acid (OA) on microRNA biogenesis.
• To determine how OA influences the interaction of RBPs with pri-miRs.
• To explore OA as a potential regulator of miR-7 processing.

Main Methods:

• Electrophoretic mobility shift assays (EMSA) were used to analyze protein-RNA interactions in HeLa cell extracts.
• In vitro processing assays were performed to assess the impact of OA on pri-miR-7 and pri-miR-16 processing.
• OA's effect on mature miR-7 production in HeLa cells was measured.

Main Results:

• Oleic acid (OA) inhibits the binding of RNA recognition motif (RRM)-containing proteins to the terminal loop of pri-miR-7.
• OA treatment disrupts pre-miR/protein complexes and rescues in vitro processing of pri-miR-7, overcoming inhibition by HuR and MSI2.
• OA reduces pri-miR-16 processing, suggesting inhibition of other necessary RRM-containing proteins, and induces mature miR-7 production in HeLa cells.

Conclusions:

• Oleic acid (OA) regulates pri-miR processing by altering protein complex formation.
• OA's ability to modulate miR-7 biogenesis provides a novel tool for RNA processing research.
• OA represents a potential lead for developing small molecules targeting the miR-7 biogenesis pathway.