ZFIN ID: ZDB-PUB-110701-1
A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity
Cifuentes, D., Xue, H., Taylor, D.W., Patnode, H., Mishima, Y., Cheloufim, S., Ma, E., Mane, S., Hannon, G.J., Lawson, N.D., Wolfe, S.A., and Giraldez, A.J.
Date: 2010
Source: Science (New York, N.Y.)   328(5986): 1694-1698 (Journal)
Registered Authors: Cifuentes, Daniel, Giraldez, Antonio, Lawson, Nathan, Mishima, Yuichiro, Wolfe, Scot A.
Keywords: none
Microarrays: GEO:GSE21503
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*
PubMed: 20448148 Full text @ Science

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.