A Novel miRNA Processing Pathway Independent of Dicer Requires Argonaute2 Catalytic Activity

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

URL: https://www.ncbi.nlm.nih.gov/pubmed/20448148
DOI: 10.1126/science.1190809

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.

Item Type: Paper
Uncontrolled Keywords: ZINC-FINGER NUCLEASES PASSENGER-STRAND RNA CLEAVAGE ZEBRAFISH SIRNAS DROSOPHILA SHRNAS SLICER
Subjects: organism description > animal > insect > Drosophila
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > shRNA
organism description > animal > fish > zebrafish
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > zinc finger proteins
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: CSHL Librarian
Date: 25 June 2010
Date Deposited: 28 Sep 2011 14:33
Last Modified: 02 Dec 2016 17:26
PMCID: PMC3093307
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15392

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