RNA Therapeutics Institute Publications

Title

A ribonuclease coordinates siRNA amplification and mRNA cleavage during RNAi

UMMS Affiliation

RNA Therapeutics Institute

Publication Date

2015-01-29

Document Type

Article

Disciplines

Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Genetics and Genomics | Therapeutics

Abstract

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.

DOI of Published Version

10.1016/j.cell.2015.01.010

Source

Cell. 2015 Jan 29;160(3):407-19. doi: 10.1016/j.cell.2015.01.010. Link to article on publisher's site

Journal/Book/Conference Title

Cell

Related Resources

Link to Article in PubMed

PubMed ID

25635455

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