A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity
- Authors
- Cifuentes, D., Xue, H., Taylor, D.W., Patnode, H., Mishima, Y., Cheloufim, S., Ma, E., Mane, S., Hannon, G.J., Lawson, N.D., Wolfe, S.A., and Giraldez, A.J.
- ID
- ZDB-PUB-110701-1
- Date
- 2010
- Source
- Science (New York, N.Y.) 328(5986): 1694-1698 (Journal)
- Registered Authors
- Cifuentes, Daniel, Giraldez, Antonio, Lawson, Nathan, Mishima, Yuichiro, Wolfe, Scot A.
- Keywords
- none
- Datasets
- GEO:GSE21503
- MeSH Terms
-
- Animals
- Argonaute Proteins
- Biocatalysis
- Embryo, Nonmammalian/metabolism
- Embryonic Development
- Erythropoiesis
- Eukaryotic Initiation Factor-2/genetics
- Eukaryotic Initiation Factor-2/metabolism*
- Humans
- MicroRNAs/chemistry*
- MicroRNAs/metabolism*
- Models, Biological
- Morphogenesis
- Nucleic Acid Conformation
- RNA Precursors/metabolism
- RNA Processing, Post-Transcriptional
- Recombinant Proteins/metabolism
- Ribonuclease III/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 20448148 Full text @ Science
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.