{"doi":"10.1093/nar/gkae1006","title":"AcrIIIA1 is a protein–RNA anti-CRISPR complex that targets core Cas and accessory nucleases","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.","journal":"Nucleic Acids Research","year":2024,"id":441493,"datarank":0.4192509541517184,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.07386319020261153,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.07386319020261153,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":9,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":true,"deposit_databanks":{"SRA":["PRJNA1039552"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1255006,"name":"Olivia Howell","orcid":null,"position":1,"is_corresponding":false},{"id":963336,"name":"Tori A. Boyle","orcid":"0000-0003-0368-1684","position":2,"is_corresponding":false},{"id":584634,"name":"Motaher Hossain","orcid":"0000-0002-9084-9686","position":3,"is_corresponding":false},{"id":297995,"name":"Forrest C. Walker","orcid":"0000-0003-4503-8734","position":4,"is_corresponding":false},{"id":1254555,"name":"Emma K. Sheriff","orcid":"0000-0001-7751-9589","position":5,"is_corresponding":false},{"id":1181410,"name":"Barbaros Aslan","orcid":"0000-0002-5233-7620","position":6,"is_corresponding":false},{"id":692672,"name":"Asma Hatoum-Aslan","orcid":"0000-0003-2395-8900","position":7,"is_corresponding":false},{"id":998154,"name":"Lucy Chou-Zheng","orcid":"0000-0003-0950-3539","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T02:01:11.152920Z","pmid":"39551936","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}