Projects per year
Abstract
CRISPR systems are widespread in the prokaryotic world, providing adaptive immunity against mobile genetic elements1,2. Type III CRISPR systems, with the signature gene cas10,
use CRISPR RNA to detect non-self RNA, activating the enzymatic Cas10
subunit to defend the cell against mobile genetic elements either
directly, via the integral histidine–aspartate (HD) nuclease domain3,4,5 or indirectly, via synthesis of cyclic oligoadenylate second messengers to activate diverse ancillary effectors6,7,8,9.
A subset of type III CRISPR systems encode an uncharacterized
CorA-family membrane protein and an associated NrN family
phosphodiesterase that are predicted to function in antiviral defence.
Here we demonstrate that the CorA-associated type III-B (Cmr) CRISPR
system from Bacteroides fragilis provides immunity against mobile genetic elements when expressed in Escherichia coli. However, B. fragilis Cmr does not synthesize cyclic oligoadenylate species on activation, instead generating S-adenosyl
methionine (SAM)-AMP (SAM is also known as AdoMet) by conjugating ATP
to SAM via a phosphodiester bond. Once synthesized, SAM-AMP binds to the
CorA effector, presumably leading to cell dormancy or death by
disruption of the membrane integrity. SAM-AMP is degraded by
CRISPR-associated phosphodiesterases or a SAM-AMP lyase, potentially
providing an ‘off switch’ analogous to cyclic oligoadenylate-specific
ring nucleases10.
SAM-AMP thus represents a new class of second messenger for antiviral
signalling, which may function in different roles in diverse cellular
contexts.
Original language | English |
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Pages (from-to) | 826-833 |
Number of pages | 22 |
Journal | Nature |
Volume | 622 |
Issue number | 7984 |
Early online date | 18 Oct 2023 |
DOIs | |
Publication status | Published - 26 Oct 2023 |
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Dissecting Molecular Biology of Cyclic: Dissecting the Molecular Biology of Cyclic Oligoadenylate Signalling
White, M. (PI) & Gloster, T. (CoI)
1/01/20 → 31/12/23
Project: Standard
Datasets
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Antiviral type III CRISPR signalling via conjugation of ATP and SAM (code)
Chi, H. (Creator) & White, M. (Creator), GitHub, 2023
https://github.com/vihoikka/Cas10_prober
Dataset: Software
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Antiviral Type III Crispr signalling via conjugation of STP and AdoMet
Shirran, S. (Creator) & Chi, H. (Creator), Figshare, 2023
DOI: 10.6084/m9.figshare.c.6646859.v1, https://doi.org/10.17630/sta/799
Dataset