GSBS Student Publications

Title

Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine

Date

11-18-2006

Document Type

Article

Medical Subject Headings

Amino Acid Sequence; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Embryo, Nonmammalian; Models, Genetic; Molecular Sequence Data; Mutation; Phylogeny; Protein Binding; *RNA Interference; RNA, Helminth; RNA, Small Interfering; Recombinant Fusion Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: Cell. 2006 Nov 17;127(4):747-57. Link to article on publisher's site

DOI of Published Version

10.1016/j.cell.2006.09.033

Related Resources

Link to Article in PubMed

Journal Title

Cell

PubMed ID

17110334