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.