期刊
SCIENCE
卷 328, 期 5986, 页码 1694-1698出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1190809
关键词
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资金
- Fundacion Ramon Areces
- Human Frontier Science Program fellowship
- NIH [R01GM081602-03/03S1, R01HL093766]
- Yale Scholar program
- Pew Scholars Program in the Biomedical Sciences
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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