Projects per year
Abstract
The CRISPR system in bacteria and archaea provides adaptive immunity
against mobile genetic elements. Type III CRISPR systems detect viral
RNA, resulting in the activation of two regions of the Cas10 protein: an
HD nuclease domain (which degrades viral DNA)1,2 and a cyclase domain (which synthesizes cyclic oligoadenylates from ATP)3,4,5. Cyclic oligoadenylates in turn activate defence enzymes with a CRISPR-associated Rossmann fold domain6, sculpting a powerful antiviral response7,8,9,10 that can drive viruses to extinction7,8. Cyclic nucleotides are increasingly implicated in host–pathogen interactions11,12,13. Here we identify a new family of viral anti-CRISPR (Acr) enzymes that rapidly degrade cyclic tetra-adenylate (cA4).
The viral ring nuclease AcrIII-1 is widely distributed in archaeal and
bacterial viruses and in proviruses. The enzyme uses a previously
unknown fold to bind cA4 specifically, and a conserved active
site to rapidly cleave this signalling molecule, allowing viruses to
neutralize the type III CRISPR defence system. The AcrIII-1 family has a
broad host range, as it targets cA4 signalling molecules
rather than specific CRISPR effector proteins. Our findings highlight
the crucial role of cyclic nucleotide signalling in the conflict between
viruses and their hosts.
Original language | English |
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Pages (from-to) | 572-575 |
Number of pages | 19 |
Journal | Nature |
Volume | 577 |
Issue number | 7791 |
Early online date | 15 Jan 2020 |
DOIs | |
Publication status | Published - 23 Jan 2020 |
Keywords
- System
- Evolutionary
- Mechanism
- Space
- DNA
Fingerprint
Dive into the research topics of 'An anti-CRISPR viral ring nuclease subverts type III CRISPR immunity'. Together they form a unique fingerprint.Projects
- 2 Finished
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Cyclic oligoadenylate signalling: Cyclic oligoadenylate signalling - a new type of antiviral response
White, M. (PI)
1/01/19 → 31/12/21
Project: Standard
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Tracey Gloster: Understanding the activity and function of hexosaminidase D
Gloster, T. (PI)
1/04/18 → 30/09/21
Project: Standard
Profiles
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Tracey Gloster
Person: Academic