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

@article{citeulike:1044679, 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.}, address = {Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.}, author = {Yigit, E. and Batista, P. J. and Bei, Y. and Pang, K. M. and Chen, C. C. and Tolia, N. H. and Joshua-Tor, L. and Mitani, S. and Simard, M. J. and Mello, C. C.}, citeulike-article-id = {1044679}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cell.2006.09.033}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17110334}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17110334}, citeulike-linkout-3 = {http://www.sciencedirect.com/science/article/B6WSN-4MC1FM1-M/1/77a795b94e2ad12465c569ab2580f0db}, citeulike-linkout-4 = {http://www.wormbase.org/db/misc/paper?name=WBPaper00028800}, day = {17}, doi = {10.1016/j.cell.2006.09.033}, issn = {0092-8674}, journal = {Cell}, keywords = {argonaute, c\_elegans, rnai, small\_rnas}, month = {November}, number = {4}, pages = {747--757}, posted-at = {2008-06-02 21:04:24}, priority = {2}, title = {Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi.}, url = {http://dx.doi.org/10.1016/j.cell.2006.09.033}, volume = {127}, year = {2006} }

TY - JOUR ID - citeulike:1044679 L3 - citeulike-article-id:1044679 N2 - 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. IS - 4 JF - Cell SN - 0092-8674 AD - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. EP - 757 TI - Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi. VL - 127 SP - 747 KW - argonaute KW - c_elegans KW - rnai KW - small_rnas AU - Yigit, E AU - Batista, PJ AU - Bei, Y AU - Pang, KM AU - Chen, CC AU - Tolia, NH AU - Joshua-Tor, L AU - Mitani, S AU - Simard, MJ AU - Mello, CC PY - 2006/11/17/ UR - http://dx.doi.org/10.1016/j.cell.2006.09.033 ER -