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

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.

Pubmed ID: 20448148

Authors

  • Cifuentes D
  • Xue H
  • Taylor DW
  • Patnode H
  • Mishima Y
  • Cheloufi S
  • Ma E
  • Mane S
  • Hannon GJ
  • Lawson ND
  • Wolfe SA
  • Giraldez AJ

Journal

Science (New York, N.Y.)

Publication Data

June 25, 2010

Associated Grants

  • Agency: NCI NIH HHS, Id: P01 CA013106
  • Agency: NCI NIH HHS, Id: P01 CA013106-38
  • Agency: NIGMS NIH HHS, Id: R01 GM081602
  • Agency: NIGMS NIH HHS, Id: R01 GM081602-01
  • Agency: NIGMS NIH HHS, Id: R01 GM081602-02
  • Agency: NIGMS NIH HHS, Id: R01 GM081602-03
  • Agency: NIGMS NIH HHS, Id: R01 GM081602-03S1
  • Agency: NIGMS NIH HHS, Id: R01 GM081602-04
  • Agency: NIGMS NIH HHS, Id: R01 GM101108
  • Agency: NHLBI NIH HHS, Id: R01 HL093766
  • Agency: NHLBI NIH HHS, Id: R01 HL093766-04
  • Agency: NIGMS NIH HHS, Id: R01GM081602-03/03S1
  • Agency: NHLBI NIH HHS, Id: R01HL093766
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

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