Abstract
RNA interference (RNAi) regulates gene expression by the cleavage of messenger RNA, by mRNA degradation and by preventing protein synthesis. These effects are mediated by a ribonucleo-protein complex known as RISC (RNA-induced silencing complex. We have previously identified four Drosophila components (short interfering RNAs, Argonaute 2 (ref. 2), VIG and FXR of a RISC enzyme that degrades specific mRNAs in response to a double-stranded-RNA trigger. Here we show that Tudor-SN (tudor staphylococcal nuclease) - a protein containing five staphylococcal/micrococcal nuclease domains and a tudor domain - is a component of the RISC enzyme in Caenorhabditis elegans, Drosophila and mammals. Although Tudor-SN contains non-canonical active-site sequences, we show that purified Tudor-SN exhibits nuclease activity similar to that of other staphylococcal nucleases. Notably, both purified Tudor-SN and RISC are inhibited by a specific competitive inhibitor of micrococcal nuclease. Tudor-SN is the first RISC subunit to be identified that contains a recognizable nuclease domain, and could therefore contribute to the RNA degradation observed in RNAi.
Original language | English |
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Pages (from-to) | 411-414 |
Number of pages | 4 |
Journal | Nature |
Volume | 425 |
Issue number | 6956 |
DOIs | |
Publication status | Published - 25 Sept 2003 |
Externally published | Yes |
Keywords
- Animals
- Binding Sites
- Caenorhabditis elegans/enzymology
- Drosophila melanogaster/enzymology
- Macromolecular Substances
- Micrococcal Nuclease/chemistry
- Protein Structure, Tertiary
- RNA Interference
- RNA Processing, Post-Transcriptional
- RNA-Induced Silencing Complex/chemistry