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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hannon, Gregory J. Mane, Shrikant Cheloufi, Sihem Patnode, Heather Lawson, Nathan D. Cifuentes, Daniel Wolfe, Scot A. Mishima, Yuichiro Giraldez, Antonio J. Xue, Huiling Taylor, David W. Ma, Enbo |
| Description | Author Affiliation: Cifuentes D ( Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.) |
| 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. |
| ISSN | 00368075 |
| e-ISSN | 10959203 |
| Journal | Science |
| Issue Number | 5986 |
| Volume Number | 328 |
| Language | English |
| Publisher | American Association for the Advancement of Science (United States) |
| Publisher Date | 2010-06-25 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Eukaryotic Initiation Factor-2 Metabolism MicroRNAs Chemistry Zebrafish Proteins Zebrafish Animals Argonaute Proteins Biocatalysis Embryo, Nonmammalian Embryonic Development Erythropoiesis Genetics Models, Biological Morphogenesis Nucleic Acid Conformation RNA Precursors RNA Processing, Post-Transcriptional Recombinant Proteins Ribonuclease III Embryology Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | History and Philosophy of Science |
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