Projects per year
Abstract
The CRISPR system provides adaptive immunity against mobile genetic
elements in prokaryotes, using small CRISPR RNAs that direct effector
complexes to degrade invading nucleic acids1,2,3. Type III effector complexes were recently demonstrated to synthesize a novel second messenger, cyclic oligoadenylate, on binding target RNA4,5. Cyclic oligoadenylate, in turn, binds to and activates ribonucleases and other factors—via a CRISPR-associated Rossman-fold domain—and thereby induces in the cell an antiviral state that is important for immunity. The mechanism of the ‘off-switch’ that resets the system is not understood. Here we identify the nuclease that degrades these cyclic oligoadenylate ring molecules. This ‘ring nuclease’ is itself a protein of the CRISPR-associated Rossman-fold family, and has a metal-independent mechanism that cleaves cyclic tetraadenylate rings to generate linear diadenylate species and switches off the antiviral state. The identification of ring nucleases adds an important insight tothe CRISPR system.
elements in prokaryotes, using small CRISPR RNAs that direct effector
complexes to degrade invading nucleic acids1,2,3. Type III effector complexes were recently demonstrated to synthesize a novel second messenger, cyclic oligoadenylate, on binding target RNA4,5. Cyclic oligoadenylate, in turn, binds to and activates ribonucleases and other factors—via a CRISPR-associated Rossman-fold domain—and thereby induces in the cell an antiviral state that is important for immunity. The mechanism of the ‘off-switch’ that resets the system is not understood. Here we identify the nuclease that degrades these cyclic oligoadenylate ring molecules. This ‘ring nuclease’ is itself a protein of the CRISPR-associated Rossman-fold family, and has a metal-independent mechanism that cleaves cyclic tetraadenylate rings to generate linear diadenylate species and switches off the antiviral state. The identification of ring nucleases adds an important insight tothe CRISPR system.
Original language | English |
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Pages (from-to) | 277-280 |
Number of pages | 16 |
Journal | Nature |
Volume | 562 |
Issue number | 7726 |
Early online date | 19 Sept 2018 |
DOIs | |
Publication status | Published - 11 Oct 2018 |
Keywords
- Archaeon sulfolobus-solfataricus
- CAS systems
- Image-analysis
- Mechanism
- Classification
- Discovery
- Immunity
- RNA
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Dive into the research topics of 'Ring nucleases deactivate Type III CRISPR ribonucleases by degrading cyclic oligoadenylate'. Together they form a unique fingerprint.Projects
- 3 Finished
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CRISPR Adaption: CRISPR Adaptation- the basis for prokaryotic adaptive immunity.
White, M. (PI)
1/10/15 → 31/12/18
Project: Standard
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CSM Complex: CRISPR-mediated cleacage by the CSM complex
White, M. (PI)
31/12/14 → 30/12/17
Project: Standard
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RS Wolfson Merit Award: The CRISPR-Cas system for prokaryotic antiviral defence
White, M. (PI)
1/08/14 → 31/07/19
Project: Standard