RRC ID |
4340
|
著者 |
Yigit E, Batista PJ, Bei Y, Pang KM, Chen CC, Tolia NH, Joshua-Tor L, Mitani S, Simard MJ, Mello CC.
|
タイトル |
Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi.
|
ジャーナル |
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.
|
巻・号 |
127(4)
|
ページ |
747-57
|
公開日 |
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 |
38.637
|
引用数 |
381
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
線虫 |
tm1860
tm872
tm914
tm1195
tm894
tm1019
tm887
tm1144 |