Heme is involved in microRNA processing

Nat Struct Mol Biol. 2007 Jan;14(1):23-9. doi: 10.1038/nsmb1182. Epub 2006 Dec 10.


MicroRNAs (miRNAs) regulate the expression of a large number of protein-coding genes. Their primary transcripts (pri-miRNAs) have to undergo multiple processing steps to reach the functional form. Little is known about how the processing of miRNAs is modulated. Here we show that the RNA-binding protein DiGeorge critical region-8 (DGCR8), which is essential for the first processing step, is a heme-binding protein. The association with heme promotes dimerization of DGCR8. The heme-bound DGCR8 dimer seems to trimerize upon binding pri-miRNAs and is active in triggering pri-miRNA cleavage, whereas the heme-free monomer is much less active. A heme-binding region of DGCR8 inhibits the pri-miRNA-processing activity of the monomer. This putative autoinhibition is overcome by heme. Our finding that heme is involved in pri-miRNA processing suggests that the gene-regulation network of miRNAs and signal-transduction pathways involving heme might be connected.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Dimerization
  • Heme / chemistry
  • Heme / metabolism*
  • Hemeproteins / chemistry
  • Hemeproteins / metabolism
  • Humans
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism


  • DGCR8 protein, human
  • Hemeproteins
  • MicroRNAs
  • Proteins
  • RNA-Binding Proteins
  • Heme