Microprocessor depends on hemin to recognize the apical loop of primary microRNA

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• The Microprocessor complex, comprising DROSHA and DGCR8, is crucial for microRNA (miRNA) biogenesis.
• DGCR8 recognizes specific RNA motifs, such as the UGU motif, to ensure accurate pri-miRNA processing.
• The precise mechanism of DGCR8's selective RNA binding and Microprocessor's function remains incompletely understood.

Purpose of the Study:

• To elucidate the mechanism by which hemin influences Microprocessor activity.
• To investigate hemin's role in the selective binding of DGCR8 to pri-miRNAs.
• To determine if hemin differentially regulates miRNA maturation based on RNA sequence.

Main Methods:

• In vitro analysis of hemin's effect on the interaction between DGCR8 and pri-miRNA apical elements.
• Construction and functional analysis of a DGCR8 mutant cell line.
• Rescue experiments to validate hemin's specific effects on miRNA expression.

Main Results:

• Hemin significantly enhances the specific interaction between the DGCR8 dimer and the UGU motif on pri-miRNAs.
• This interaction boosts the efficiency and fidelity of pri-miRNA processing by the Microprocessor complex in vitro.
• Hemin selectively stimulates the expression of miRNAs containing the UGU motif in a cellular context.
• A novel function of hemin in promoting specific RNA-protein interactions is established.

Conclusions:

• Hemin acts as a molecular modulator, enhancing DGCR8's recognition of the UGU motif in pri-miRNAs.
• This mechanism allows hemin to selectively regulate miRNA maturation, impacting gene expression.
• The study reveals a new role for hemin in controlling RNA-protein interactions and miRNA biogenesis.