A self-limiting dimeric TIR effector specialised for type III CRISPR-mediated immunity
- 1University of St Andrews
Abstract
Antiviral defence systems frequently utilise cyclic nucleotide second messengers. A prominent example is the type III CRISPR-Cas system, which generates cyclic oligoadenylates (cOA) on detecting viral RNA. cOA molecules can bind and activate a wide range of effectors to provide antiviral defence. In both prokaryotes and higher plants, activation of a catalytic Toll/Interleukin Receptor (TIR) domain by multimerization results in degradation of NAD+, limiting cell metabolism and thus viral replication. Here, we describe a CRISPR-associated TIR-containing effector that includes a SAVED (SMODS-associated and fused to various effector domains) domain for nucleotide sensing and a cOA-degrading ring nuclease Crn4 domain. We demonstrate that the TIR-SAVED-Ring nuclease (TSR1) effector binds cA3, resulting in activation of the TIR NADase activity. The Crn4 domain, which imposes an unusual dimeric quaternary structure on the effector, degrades cA3, providing a mechanism to auto-deactivate the effector. TSR1 is thus a highly unusual example of a dimeric and self-limiting TIR effector in antiviral immunity.
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BibTeX
@misc{sun2026selflimiting,
title = {{A self-limiting dimeric TIR effector specialised for type III CRISPR-mediated immunity}},
author = {Y. Sun and S. McMahon and S. Snyowsky and M. F. White},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.16.751991},
url = {https://www.biorxiv.org/content/10.64898/2026.09.16.751991v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A self-limiting dimeric TIR effector specialised for type III CRISPR-mediated immunity
AU - Y. Sun
AU - S. McMahon
AU - S. Snyowsky
AU - M. F. White
PY - 2026
DA - 2026/09/16
PB - bioRxiv
DO - 10.64898/2026.09.16.751991
UR - https://www.biorxiv.org/content/10.64898/2026.09.16.751991v1
AB - Antiviral defence systems frequently utilise cyclic nucleotide second messengers. A prominent example is the type III CRISPR-Cas system, which generates cyclic oligoadenylates (cOA) on detecting viral RNA. cOA molecules can bind and activate a wide range of effectors to provide antiviral defence. In both prokaryotes and higher plants, activation of a catalytic Toll/Interleukin Receptor (TIR) domain by multimerization results in degradation of NAD+, limiting cell metabolism and thus viral replication. Here, we describe a CRISPR-associated TIR-containing effector that includes a SAVED (SMODS-associated and fused to various effector domains) domain for nucleotide sensing and a cOA-degrading ring nuclease Crn4 domain. We demonstrate that the TIR-SAVED-Ring nuclease (TSR1) effector binds cA3, resulting in activation of the TIR NADase activity. The Crn4 domain, which imposes an unusual dimeric quaternary structure on the effector, degrades cA3, providing a mechanism to auto-deactivate the effector. TSR1 is thus a highly unusual example of a dimeric and self-limiting TIR effector in antiviral immunity.
ER -