期刊
CELL REPORTS
卷 5, 期 3, 页码 715-726出版社
CELL PRESS
DOI: 10.1016/j.celrep.2013.09.029
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资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [21115002]
- March of Dimes
- Pew Scholar
- National Institutes of Health (NIH) [R01GM101108, R01GM102251, R21HD073768]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development-NIH [K99HD071968]
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [22227006, 21115002] Funding Source: KAKEN
MicroRNAs (miRNAs) are typically generated as similar to 22-nucleotide double-stranded RNAs via the processing of precursor hairpins by the ribonuclease III enzyme Dicer, after which they are loaded into Argonaute (Ago) proteins to form an RNA-induced silencing complex (RISC). However, the biogenesis of miR-451, an erythropoietic miRNA conserved in vertebrates, occurs independently of Dicer and instead requires cleavage of the 3' arm of the pre-miR-451 precursor hairpin by Ago2. The 3' end of the Ago2-cleaved pre-miR-451 intermediate is then trimmed to the mature length by an unknown nuclease. Here, using a classical chromatographic approach, we identified poly(A)-specific ribonuclease (PARN) as the enzyme responsible for the 3'-5' exonucleolytic trimming of Ago2-cleaved pre-miR-451. Surprisingly, our data show that trimming of Ago2-cleaved precursor miRNAs is not essential for target silencing, indicating that RISC is functional with miRNAs longer than the mature length. Our findings define the maturation step in the miRNA biogenesis pathway that depends on Ago2-mediated cleavage.
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