Cifuentes, D., Xue, H. L., Taylor, D. W., Patnode, H., Mishima, Y., Cheloufi, S., Ma, E. B., Mane, S., Hannon, G. J., Lawson, N. D., Wolfe, S. A., Giraldez, A. J. (June 2010) A Novel miRNA Processing Pathway Independent of Dicer Requires Argonaute2 Catalytic Activity. Science, 328 (5986). pp. 1694-1698. ISSN 0036-8075
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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.
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