A ribonuclease coordinates siRNA amplification and mRNA cleavage during RNAi
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Authors
Tsai, Hsin-YueChen, Chun-Chieh G.
Conte, Darryl Jr.
Moresco, James J.
Chaves, Daniel A.
Mitani, Shohei
Yates, John R. 3rd
Tsai, Ming-Daw
Mello, Craig C.
UMass Chan Affiliations
RNA Therapeutics InstituteDocument Type
Journal ArticlePublication Date
2015-01-29Keywords
Biochemistry, Biophysics, and Structural BiologyCell and Developmental Biology
Genetics and Genomics
Therapeutics
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Show full item recordAbstract
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 3' 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 3' uridylated mRNA fragments to serve as templates for the RdRP-directed amplification of the silencing signal.Source
Cell. 2015 Jan 29;160(3):407-19. doi: 10.1016/j.cell.2015.01.010. Link to article on publisher's site
DOI
10.1016/j.cell.2015.01.010Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48815PubMed ID
25635455Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.cell.2015.01.010