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, 127 (4), 747-57

Analysis of the C. Elegans Argonaute Family Reveals That Distinct Argonautes Act Sequentially During RNAi

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Analysis of the C. Elegans Argonaute Family Reveals That Distinct Argonautes Act Sequentially During RNAi

Erbay Yigit et al. 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.

Comment in

  • Knocking Out the Argonautes
    FA Steiner et al. Cell 127 (4), 667-8. PMID 17110324.
    Argonaute proteins are key players in gene silencing involving small RNAs. In this issue, Yigit et al. (2006) report a comprehensive study of Argonautes in the worm that …

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