Analysis of the C-elegans argonaute family reveals that distinct argonautes act sequentially during RNAi

被引：473

作者：

Yigit, Erbay

Batista, Pedro J.

Bei, Yanxia

Pang, Ka Min

Chen, Chun-Chieh G.

Tolia, Niraj H.

Joshua-Tor, Leemor

Mitani, Shohei

Simard, Martin J. ^{[1
]}

Mello, Craig C.

机构：

[1] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA

[2] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA

[3] Gulbenkian PHD Programme Biomed, P-2780156 Oeiras, Portugal

[4] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA

[5] Tokyo Womens Med Univ, Sch Med, Dept Physiol, Tokyo 1628666, Japan

[6] Japan Sci & Technol Agcy, CREST, Tokyo 1628666, Japan

来源：

CELL | 2006年 / 127卷 / 04期

关键词：

D O I：

10.1016/j.cell.2006.09.033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：747 / 757

页数：11

共 48 条

[1] A novel class of small RNAs bind to MILI protein in mouse testes
Aravin, Alexei
Gaidatzis, Dimos
Pfeffer, Sebastien
Lagos-Quintana, Mariana
Landgraf, Pablo
Iovino, Nicola
Morris, Patricia
Brownstein, Michael J.
Kuramochi-Miyagawa, Satomi
Nakano, Toru
Chien, Minchen
Russo, James J.
Ju, Jingyue
Sheridan, Robert
Sander, Chris
Zavolan, Mihaela
Tuschl, Thomas
[J]. NATURE, 2006, 442 (7099) : 203 - 207
[2] BRENNER S, 1974, GENETICS, V77, P71
[3] RNase III enzymes and the initiation of gene silencing
Carmell, MA
Hannon, GJ
[J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2004, 11 (03) : 214 - 218
[4] The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis
Carmell, MA
Xuan, ZY
Zhang, MQ
Hannon, GJ
[J]. GENES & DEVELOPMENT, 2002, 16 (21) : 2733 - 2742
[5] A member of the polymerase β nucleotidyltransferase superfamily is required for RNA interference in C-elegans
Chen, CCG
Simard, MJ
Tabara, H
Brownell, DR
McCollough, JA
Mello, CC
[J]. CURRENT BIOLOGY, 2005, 15 (04) : 378 - 383
[6] TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing
Chendrimada, TP
Gregory, RI
Kumaraswamy, E
Norman, J
Cooch, N
Nishikura, K
Shiekhattar, R
[J]. NATURE, 2005, 436 (7051) : 740 - 744
[7] A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal
Cox, DN
Chao, A
Baker, J
Chang, L
Qiao, D
Lin, HF
[J]. GENES & DEVELOPMENT, 1998, 12 (23) : 3715 - 3727
[8] miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis
Deng, W
Lin, HF
[J]. DEVELOPMENTAL CELL, 2002, 2 (06) : 819 - 830
[9] Duchaine TF, 2006, CELL, V124, P343, DOI [10.1016/j.cell.2005.11.036, 10.1016/j.cel.2005.11.036]
[10] Evans T.C., 2006, TRANSFORMATION MICRO, V10, P1, DOI [DOI 10.1895/WORMBOOK.1.108.1, 10.1895/wormbook.1.108.1]

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