RT Journal Article SR Electronic T1 A Novel miRNA Processing Pathway Independent of Dicer Requires Argonaute2 Catalytic Activity JF Science JO Science FD American Association for the Advancement of Science SP 1694 OP 1698 DO 10.1126/science.1190809 VO 328 IS 5986 A1 Cifuentes, Daniel A1 Xue, Huiling A1 Taylor, David W. A1 Patnode, Heather A1 Mishima, Yuichiro A1 Cheloufi, Sihem A1 Ma, Enbo A1 Mane, Shrikant A1 Hannon, Gregory J. A1 Lawson, Nathan D. A1 Wolfe, Scot A. A1 Giraldez, Antonio J. YR 2010 UL http://science.sciencemag.org/content/328/5986/1694.abstract 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.