RRC ID 45914
Author Tsai HY, Chen CC, Conte D Jr, Moresco JJ, Chaves DA, Mitani S, Yates JR 3rd, Tsai MD, Mello CC.
Title A ribonuclease coordinates siRNA amplification and mRNA cleavage during RNAi.
Journal Cell
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.
Volume 160(3)
Pages 407-19
Published 2015-1-29
DOI 10.1016/j.cell.2015.01.010
PII S0092-8674(15)00011-2
PMID 25635455
PMC PMC4318647
MeSH Amino Acid Sequence Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cytoplasmic Granules / metabolism Endoribonucleases / chemistry Endoribonucleases / genetics Endoribonucleases / metabolism* Molecular Sequence Data RNA Interference RNA, Double-Stranded RNA, Messenger / metabolism RNA, Small Interfering / metabolism RNA-Dependent RNA Polymerase / metabolism Ribonuclease III / metabolism Sequence Alignment
IF 38.637
Times Cited 25
C.elegans tm2252 tm2192 tm5004 tm5149 tm4844 tm1358 tm3748