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Post-transcriptional control of DGCR8 expression by the Microprocessor

Robinson Triboulet, Hao-Ming Chang, Robert J Lapierre

    RNA (New York, N.Y.)
    |April 23, 2009
    PubMed

    Insights

    The Microprocessor complex, essential for microRNA biogenesis, negatively regulates DGCR8 expression through cleavage of a hairpin in the DGCR8 mRNA 5'UTR, revealing a novel feedback loop.

    Area of Science:

    • Molecular Biology
    • Gene Regulation

    Background:

    • MicroRNA (miRNA) biogenesis is crucial for cellular function and relies on the Microprocessor complex, containing RNase III Drosha and DGCR8.
    • The precise regulatory mechanisms governing Drosha and DGCR8 protein expression remain largely uncharacterized.

    Discussion:

    • This study identifies a negative feedback loop where the Microprocessor complex directly regulates DGCR8 expression.
    • Cleavage of a specific hairpin structure within the DGCR8 mRNA 5' untranslated region (5'UTR) by the Microprocessor complex mediates this regulation.

    Key Insights:

    • Knockdown of Drosha results in elevated DGCR8 mRNA and protein levels, supporting Microprocessor-dependent repression.
    • The DGCR8 5'UTR confers Microprocessor-dependent repression on a luciferase reporter gene in vivo, confirming the functional role of this regulatory element.

    Outlook:

    • This discovery elucidates a novel regulatory mechanism controlling DGCR8 levels, impacting miRNA biogenesis.
    • Further research can explore the implications of this feedback loop in various biological contexts and diseases.

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