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PMID:17110334
| Citation |
Yigit, E, Batista, PJ, Bei, Y, Pang, KM, Chen, CC, Tolia, NH, Joshua-Tor, L, Mitani, S, Simard, MJ and Mello, CC (2006) Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi. Cell 127:747-57 |
|---|---|
| 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. |
| Links |
PubMed Online version:10.1016/j.cell.2006.09.033 |
| Keywords |
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 |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
CAEEL:G5EEH0 |
enables |
GO:0035197: siRNA binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
|
CAEEL:G5EEH0 |
part_of |
GO:0016442: RISC complex |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
CAEEL:P90786 |
involved_in |
GO:0000003: reproduction |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
involved_in |
GO:0016246: RNA interference |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
| GO:1900369: negative regulation of RNA interference |
IMP: Inferred from Mutant Phenotype: |
P |
Figure 4A |
complete |
| |||
| GO:1900369: negative regulation of RNA interference |
IMP: Inferred from Mutant Phenotype: |
P |
Seeded From UniProt |
complete |
| |||
|
involved_in |
GO:0016246: RNA interference |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0000070: mitotic sister chromatid segregation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0016246: RNA interference |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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