RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex

EMBO Rep. 2007 Aug;8(8):763-9. doi: 10.1038/sj.embor.7401011. Epub 2007 Jun 22.

Abstract

MicroRNAs (miRNAs) mediate translational repression or degradation of their target messenger RNAs by RNA interference (RNAi). The primary transcripts of miRNA genes (pri-miRNAs) are sequentially processed by the nuclear Drosha-DGCR8 complex to approximately 60-70 nucleotide (nt) intermediates (pre-miRNAs) and then by the cytoplasmic Dicer-TRBP complex to approximately 20-22 nt mature miRNAs. Certain pri-miRNAs are subject to RNA editing that converts adenosine to inosine (A --> I RNA editing); however, the fate of edited pri-miRNAs is mostly unknown. Here, we provide evidence that RNA editing of pri-miR-151 results in complete blockage of its cleavage by Dicer and accumulation of edited pre-miR-151 RNAs. Our results indicate that A --> I conversion at two specific positions of the pre-miRNA foldback structure can affect its interaction with the Dicer-TRBP complex, showing a new regulatory role of A --> I RNA editing in miRNA biogenesis.

Publication types

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

MeSH terms

  • Adenosine Deaminase / genetics
  • Animals
  • Base Sequence
  • Brain / metabolism
  • Humans
  • Mice
  • Mice, Mutant Strains
  • MicroRNAs / chemistry
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • RNA Editing*
  • RNA Precursors / chemistry
  • RNA Precursors / metabolism
  • RNA-Binding Proteins
  • Ribonuclease III / chemistry
  • Ribonuclease III / metabolism*

Substances

  • MIRN151 microRNA, mouse
  • MicroRNAs
  • RNA Precursors
  • RNA-Binding Proteins
  • Ribonuclease III
  • ADARB1 protein, human
  • Adenosine Deaminase