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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbergkae1006
Pages (from-to)13490-13514
Number of pages25
JournalNucleic acids research
Volume52
Issue number22
Early online dateNov 18 2024
DOIs
StatePublished - Dec 11 2024

ASJC Scopus subject areas

  • Genetics

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