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Updated: Jul 18, 2026

A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells
06:48

A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells

Published on: June 16, 2022

Heme is involved in microRNA processing

Michael Faller1, Michio Matsunaga, Sheng Yin

  • 1Department of Biological Chemistry, David Geffen School of Medicine, University of California at Los Angeles (UCLA), Los Angeles, California 90095, USA.

Nature Structural & Molecular Biology
|December 13, 2006
PubMed

Insights

The RNA-binding protein DGCR8, crucial for microRNA (miRNA) processing, binds heme. Heme binding promotes DGCR8 dimerization and activation, linking miRNA gene regulation with heme signaling pathways.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression.
  • pri-miRNA processing is essential for miRNA maturation but poorly understood.
  • DGCR8 is a critical protein for the initial step of miRNA processing.

Purpose of the Study:

  • To investigate the regulatory mechanisms of pri-miRNA processing.
  • To determine the role of DGCR8 in miRNA biogenesis.
  • To explore potential connections between miRNA regulation and heme signaling.

Main Methods:

  • Biochemical assays to test DGCR8's interaction with heme.
  • Analysis of DGCR8 dimerization and oligomerization states.
  • In vitro assays to measure pri-miRNA cleavage activity.

Main Results:

  • DGCR8 is identified as a heme-binding protein.
  • Heme binding induces DGCR8 dimerization and enhances its activity in pri-miRNA cleavage.
  • A heme-binding region in DGCR8 appears to autoinhibit its monomeric form, an inhibition relieved by heme.
  • Heme-bound DGCR8 dimers may trimerize upon pri-miRNA binding to facilitate cleavage.

Conclusions:

  • Heme is a novel regulator of DGCR8 function in miRNA processing.
  • The findings reveal a mechanism of DGCR8 activation by heme, involving dimerization and potentially trimerization.
  • This study suggests a functional link between miRNA biogenesis pathways and cellular heme-sensing mechanisms.

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