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

Autor:	Chou-Zheng L; Department of Microbiology, University of Illinois, 601 S. Goodwin Avenue, Urbana, IL 61801, USA., Howell O; Department of Microbiology, University of Illinois, 601 S. Goodwin Avenue, Urbana, IL 61801, USA., Boyle TA; Department of Microbiology, University of Illinois, 601 S. Goodwin Avenue, Urbana, IL 61801, USA., Hossain M; Department of Microbiology, University of Illinois, 601 S. Goodwin Avenue, Urbana, IL 61801, USA., Walker FC; Department of Biological Sciences, University of Alabama, 1325 Hackberry Lane, Tuscaloosa, AL 35401, USA., Sheriff EK; Department of Biological Sciences, University of Alabama, 1325 Hackberry Lane, Tuscaloosa, AL 35401, USA., Aslan B; Department of Microbiology, University of Illinois, 601 S. Goodwin Avenue, Urbana, IL 61801, USA., Hatoum-Aslan A; Department of Microbiology, University of Illinois, 601 S. Goodwin Avenue, Urbana, IL 61801, USA.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Nov 18. Date of Electronic Publication: 2024 Nov 18.
DOI:	10.1093/nar/gkae1006
Abstrakt:	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. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu