PT  - JOURNAL ARTICLE
AU  - Cifuentes, Daniel
AU  - Xue, Huiling
AU  - Taylor, David W.
AU  - Patnode, Heather
AU  - Mishima, Yuichiro
AU  - Cheloufi, Sihem
AU  - Ma, Enbo
AU  - Mane, Shrikant
AU  - Hannon, Gregory J.
AU  - Lawson, Nathan D.
AU  - Wolfe, Scot A.
AU  - Giraldez, Antonio J.
TI  - A Novel miRNA Processing Pathway Independent of Dicer Requires Argonaute2 Catalytic Activity
AID  - 10.1126/science.1190809
DP  - 2010 Jun 25
TA  - Science
PG  - 1694--1698
VI  - 328
IP  - 5986
4099  - http://science.sciencemag.org/content/328/5986/1694.short
4100  - http://science.sciencemag.org/content/328/5986/1694.full
SO  - Science2010 Jun 25; 328
AB  - 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.