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

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

Author information

1
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.

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.

PMID:
20448148
PMCID:
PMC3093307
DOI:
10.1126/science.1190809
[Indexed for MEDLINE]
Free PMC Article

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