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

Science (New York, N.Y.) | Jun 25, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20448148

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 RIS Download

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

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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:

ZFIN (Data, Gene Expression)

GO (Data, Gene Annotation)

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