Argonaute2 is the catalytic engine of mammalian RNAi

Liu, J., Carmell, M. A., Rivas, F. V., Marsden, C. G., Thomson, J. M., Song, J. J., Hammond, S. M., Joshua-Tor, L., Hannon, G. J. (September 2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science, 305 (5689). pp. 1437-41. ISSN 1095-9203 (Electronic)

URL: http://www.ncbi.nlm.nih.gov/pubmed/15284456
DOI: 10.1126/science.1102513

Abstract

Gene silencing through RNA interference (RNAi) is carried out by RISC, the RNA-induced silencing complex. RISC contains two signature components, small interfering RNAs (siRNAs) and Argonaute family proteins. Here, we show that the multiple Argonaute proteins present in mammals are both biologically and biochemically distinct, with a single mammalian family member, Argonaute2, being responsible for messenger RNA cleavage activity. This protein is essential for mouse development, and cells lacking Argonaute2 are unable to mount an experimental response to siRNAs. Mutations within a cryptic ribonuclease H domain within Argonaute2, as identified by comparison with the structure of an archeal Argonaute protein, inactivate RISC. Thus, our evidence supports a model in which Argonaute contributes "Slicer" activity to RISC, providing the catalytic engine for RNAi.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Animals Catalysis Cell Line Cells Cultured Central Nervous System embryology Embryonic and Fetal Development Gene Expression Profiling Gene Expression Regulation Developmental Humans In Situ Hybridization Mice MicroRNAs metabolism Molecular Sequence Data Mutagenesis Insertional Oligonucleotide Array Sequence Analysis Peptide Initiation Factors chemistry metabolism Point Mutation RNA Interference RNA Double-Stranded RNA Messenger metabolism RNA Small Interfering metabolism RNA-Induced Silencing Complex chemistry metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene silencing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > siRNA
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL labs > Joshua-Tor lab
Watson School > Publications
Depositing User: CSHL Librarian
Date: 3 September 2004
Date Deposited: 01 Feb 2012 14:31
Last Modified: 19 Sep 2014 15:04
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22426

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