RRC ID 4340
Author Yigit E, Batista PJ, Bei Y, Pang KM, Chen CC, Tolia NH, Joshua-Tor L, Mitani S, Simard MJ, Mello CC.
Title Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi.
Journal Cell
Abstract Argonaute (AGO) proteins interact with small RNAs to mediate gene silencing. C. elegans contains 27 AGO genes, raising the question of what roles these genes play in RNAi and related gene-silencing pathways. Here we describe 31 deletion alleles representing all of the previously uncharacterized AGO genes. Analysis of single- and multiple-AGO mutant strains reveals functions in several pathways, including (1) chromosome segregation, (2) fertility, and (3) at least two separate steps in the RNAi pathway. We show that RDE-1 interacts with trigger-derived sense and antisense RNAs to initiate RNAi, while several other AGO proteins interact with amplified siRNAs to mediate downstream silencing. Overexpression of downstream AGOs enhances silencing, suggesting that these proteins are limiting for RNAi. Interestingly, these AGO proteins lack key residues required for mRNA cleavage. Our findings support a two-step model for RNAi, in which functionally and structurally distinct AGOs act sequentially to direct gene silencing.
Volume 127(4)
Pages 747-57
Published 2006-11-17
DOI 10.1016/j.cell.2006.09.033
PII S0092-8674(06)01293-1
PMID 17110334
MeSH Amino Acid Sequence Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / metabolism* Embryo, Nonmammalian / cytology Models, Genetic Molecular Sequence Data Mutation / genetics Phylogeny Protein Binding RNA Interference* RNA, Helminth / metabolism RNA, Small Interfering / metabolism Recombinant Fusion Proteins / metabolism
IF 36.216
Times Cited 309
C.elegans tm1860 tm872 tm914 tm1195 tm894 tm1019 tm887 tm1144