{"doi":"10.1101/2022.06.22.497266","title":"Molecular Mechanism of Active Cas7-11 in Processing CRISPR RNA and Interfering Target RNA","abstract":"Abstract Cas7-11 is a Type III-E CRISPR Cas effector that confers programmable RNA cleavage and has potential applications in RNA interference. Cas7-11 encodes a single polypeptide containing four Cas7- and one Cas11-like segments that obscures the distinction between the multi-subunit Class 1 and the single-subunit Class-2 CRISPR-Cas systems. We report a cryo-EM structure of the active Cas7-11 from Desulfonema ishimotonii (DiCas7-11) that reveals the molecular basis for RNA processing and interference activities. DiCas7-11 arranges its Cas7- and Cas11-like domains in an extended form that resembles the backbone made up by four Cas7 and one Cas11 subunits in the multi-subunit enzymes. Unlike the multi-subunit enzymes, however, the backbone of DiCas7-11 contains evolutionarily different Cas7 and Cas11 domains, giving rise to their unique functionality. The first Cas7-like domain nearly engulfs the last 15 direct repeat nucleotides and is responsible for processing and recognition of the CRISPR RNA. Whereas both the second and the third Cas7-like domains mediate target RNA cleavage, they differ in metal requirement for catalysis. The long variable insertion to the fourth Cas7-like domain has little impact to RNA processing or targeting, suggesting the possibility for engineering a compact and programmable RNA interference tool. One Sentence Summary Structures of Cas7-11 reveal the molecular basis for processing CRISPR RNA and for cleaving target RNA.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":309478,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":367590,"name":"Jay Rai","orcid":"0000-0002-4473-3850","position":1,"is_corresponding":false},{"id":482417,"name":"Anuska Das","orcid":"0000-0002-8014-8915","position":2,"is_corresponding":false},{"id":482420,"name":"Hong Li","orcid":"0000-0003-2046-9861","position":3,"is_corresponding":false},{"id":1004788,"name":"Hemant Gowswami","orcid":null,"position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T00:33:11.579763Z","pmid":null,"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":[]}