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AcrIIIA1是一种蛋白质-RNA抗CRISPR复合物，其靶向核心Cas和辅助核酸酶。

AcrIIIA1 is a protein-RNA anti-CRISPR complex that targets core Cas and accessory nucleases.

作者信息

Chou-Zheng Lucy, Howell Olivia, Boyle Tori A, Hossain Motaher, Walker Forrest C, Sheriff Emma K, Aslan Barbaros, Hatoum-Aslan Asma

机构信息

Department of Microbiology, University of Illinois, 601 S. Goodwin Avenue, Urbana, IL 61801, USA.

Department of Biological Sciences, University of Alabama, 1325 Hackberry Lane, Tuscaloosa, AL 35401, USA.

出版信息

Nucleic Acids Res. 2024 Dec 11;52(22):13490-13514. doi: 10.1093/nar/gkae1006.

DOI:10.1093/nar/gkae1006
PMID:39551936
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11662646/
Abstract

Clustered regularly-interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins protect bacteria and archaea from their viruses, and anti-CRISPRs (Acrs) are small virus-encoded proteins that inhibit CRISPR-Cas immunity. Over 80 families of Acrs have been described to date; however, only three of these subvert Type III CRISPR-Cas immunity. Type III systems employ a complex network of Cas and accessory nucleases to degrade viral nucleic acids. Here, we discover and characterize AcrIIIA1, the first Type III-A specific anti-CRISPR protein. We demonstrate that AcrIIIA1 binds to Csm2 within the Cas10-Csm effector complex and attenuates Cas10's DNase activity and second messenger production. Additionally, AcrIIIA1 associates with fragmented t(m)RNAs (acrIIIA1-RNAs), and we show that they co-purify with the Cas10-Csm complex during phage infection. Although the precise role(s) of acrIIIA1-RNAs remain unclear, we found that they bind stably to RNase R, a host-encoded nuclease known to bolster immunity, and RNase R has the capacity to degrade them. Altogether, our results support a model in which AcrIIIA1 and its associated RNAs target both core Cas and accessory nucleases to provide robust protection against Type III CRISPR-Cas immunity.

摘要

成簇规律间隔短回文重复序列（CRISPRs）和CRISPR相关（Cas）蛋白可保护细菌和古生菌免受病毒侵害，而抗CRISPR（Acr）是病毒编码的小蛋白，可抑制CRISPR-Cas免疫。迄今为止，已描述了80多个Acr家族；然而，其中只有三个能破坏III型CRISPR-Cas免疫。III型系统利用复杂的Cas和辅助核酸酶网络来降解病毒核酸。在此，我们发现并表征了AcrIIIA1，这是首个III-A型特异性抗CRISPR蛋白。我们证明AcrIIIA1与Cas10-Csm效应复合物中的Csm2结合，并减弱Cas10的DNA酶活性和第二信使的产生。此外，AcrIIIA1与片段化的t（m）RNA（acrIIIA1-RNA）相关联，并且我们表明在噬菌体感染期间它们与Cas10-Csm复合物共纯化。尽管acrIIIA1-RNA的确切作用尚不清楚，但我们发现它们与RNase R稳定结合，RNase R是一种已知可增强免疫力的宿主编码核酸酶，并且RNase R有能力降解它们。总之，我们的结果支持了一个模型，即AcrIIIA1及其相关RNA靶向核心Cas和辅助核酸酶，以提供针对III型CRISPR-Cas免疫的强大保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/4c54002276b1/gkae1006fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/c00d76700120/gkae1006figgra1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/592e81eb3f46/gkae1006fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/35f0d0532650/gkae1006fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/e7a0ff26bfe5/gkae1006fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/188242635ce7/gkae1006fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/8527de528ea1/gkae1006fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/28f142ee171b/gkae1006fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/56cf5064fc06/gkae1006fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/4c54002276b1/gkae1006fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/c00d76700120/gkae1006figgra1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/592e81eb3f46/gkae1006fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/35f0d0532650/gkae1006fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/e7a0ff26bfe5/gkae1006fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/188242635ce7/gkae1006fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/8527de528ea1/gkae1006fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/28f142ee171b/gkae1006fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/56cf5064fc06/gkae1006fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30a/11662646/4c54002276b1/gkae1006fig8.jpg

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