期刊
CELL
卷 160, 期 3, 页码 407-419出版社
CELL PRESS
DOI: 10.1016/j.cell.2015.01.010
关键词
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资金
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- Leukemia and Lymphoma Society [5247-09]
- National Center for Research Resources [5P41RR011823]
- National Institute on Aging [R01AG027463]
- National Institute of General Medical Sciences [8P41GM103533]
- Fundacao para Ciencia e a Tecnologia, Portugal [SFRH/BD/17629/2004/H6BM]
- Academia Sinica
- NIH [GM058800, 1S10RR027052]
- Grants-in-Aid for Scientific Research [24390053] Funding Source: KAKEN
- Fundação para a Ciência e a Tecnologia [SFRH/BD/17629/2004] Funding Source: FCT
Effective silencing by RNA-interference (RNAi) depends on mechanisms that amplify and propagate the silencing signal. In some organisms, small-interfering RNAs (siRNAs) are amplified from target mRNAs by RNA-dependent RNA polymerase (RdRP). Both RdRP recruitment and mRNA silencing require Argonaute proteins, which are generally thought to degrade RNAi targets by directly cleaving them. However, in C. elegans, the enzymatic activity of the primary Argonaute, RDE-1, is not required for silencing activity. We show that RDE-1 can instead recruit an endoribonuclease, RDE-8, to target RNA. RDE-8 can cleave RNA in vitro and is needed for the production of 30 uridylated fragments of target mRNA in vivo. We also find that RDE-8 promotes RdRP activity, thereby ensuring amplification of siRNAs. Together, our findings suggest a model in which RDE-8 cleaves target mRNAs to mediate silencing, while generating 30 uridylated mRNA fragments to serve as templates for the RdRP-directed amplification of the silencing signal.
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