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)
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 School of Biological Sciences > 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: | https://repository.cshl.edu/id/eprint/22426 |
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