title: A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity.
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.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cifuentes
authors.forename: Huiling
authors.initials: H
authors.lastname: Xue
authors.forename: David W
authors.initials: DW
authors.lastname: Taylor
authors.forename: Heather
authors.initials: H
authors.lastname: Patnode
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Mishima
authors.forename: Sihem
authors.initials: S
authors.lastname: Cheloufi
authors.forename: Enbo
authors.initials: E
authors.lastname: Ma
authors.forename: Shrikant
authors.initials: S
authors.lastname: Mane
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Lawson
authors.forename: Scot A
authors.initials: SA
authors.lastname: Wolfe
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Giraldez
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D055162:Biocatalysis; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D004920:Erythropoiesis; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D009024:Morphogenesis; D009690:Nucleic Acid Conformation; D012322:RNA Precursors / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D011994:Recombinant Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C466422:AGO2 protein, human; C550569:Ago2 protein, zebrafish; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D035683:MicroRNAs; C539470:Mirn451 microRNA, zebrafish; D012322:RNA Precursors; D011994:Recombinant Proteins; D029961:Zebrafish Proteins; D043244:Ribonuclease III
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