Analysis of the C. elegans Argonaute Family Reveals that Distinct Argonautes Act Sequentially during RNAi
CellPublished 1 November 2006Open access
Erbay Yigit, Pedro J. Batista, Yanxia Bei, Ka Ming Pang, Chun-Chieh G. Chen, Niraj H. Tolia
Citations687
SJR quartileQ1
SJR score22.61
SNIP7.62
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TL;DR
Analysis of single- and multiple-AGO mutant strains reveals functions in several pathways, including chromosome segregation, fertility, and at least two separate steps in the RNAi pathway, supporting a two-step model for RNAi.
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.
Keywords
Biochemistry, Genetics and Molecular Biology
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