A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity

Science. 2010 Jun 25;328(5986):1694-8. doi: 10.1126/science.1190809. Epub 2010 May 6.

Abstract

Dicer is a central enzyme in microRNA (miRNA) processing. We identified a Dicer-independent miRNA biogenesis pathway that uses Argonaute2 (Ago2) slicer catalytic activity. In contrast to other miRNAs, miR-451 levels were refractory to dicer loss of function but were reduced in MZago2 (maternal-zygotic) mutants. We found that pre-miR-451 processing requires Ago2 catalytic activity in vivo. MZago2 mutants showed delayed erythropoiesis that could be rescued by wild-type Ago2 or miR-451-duplex but not by catalytically dead Ago2. Changing the secondary structure of Dicer-dependent miRNAs to mimic that of pre-miR-451 restored miRNA function and rescued developmental defects in MZdicer mutants, indicating that the pre-miRNA secondary structure determines the processing pathway in vivo. We propose that Ago2-mediated cleavage of pre-miRNAs, followed by uridylation and trimming, generates functional miRNAs independently of Dicer.

Publication types

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

MeSH terms

  • Animals
  • Argonaute Proteins
  • Biocatalysis
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development
  • Erythropoiesis
  • Eukaryotic Initiation Factor-2 / genetics
  • Eukaryotic Initiation Factor-2 / metabolism*
  • Humans
  • MicroRNAs / chemistry*
  • MicroRNAs / metabolism*
  • Models, Biological
  • Morphogenesis
  • Nucleic Acid Conformation
  • RNA Precursors / metabolism
  • RNA Processing, Post-Transcriptional
  • Recombinant Proteins / metabolism
  • Ribonuclease III / metabolism
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*

Substances

  • AGO2 protein, human
  • Ago2 protein, zebrafish
  • Argonaute Proteins
  • Eukaryotic Initiation Factor-2
  • MicroRNAs
  • Mirn451 microRNA, zebrafish
  • RNA Precursors
  • Recombinant Proteins
  • Zebrafish Proteins
  • Ribonuclease III

Associated data

  • GEO/GSE21503