{"doi":"10.1016/j.omtn.2024.102190","title":"Expanding RNA editing toolkit using an IDR-based strategy","abstract":"RNA base editors should ideally be free of immunogenicity, compact, efficient, and specific, which has not been achieved for C > U editing. Here we first describe a compact C > U editor entirely of human origin, created by fusing the human C > U editing enzyme RESCUE-S to Cas inspired RNA targeting system (CIRTS), a tiny, human-originated programmable RNA-binding domain. This editor, CIRTS-RESCUEv1 (V1), was inefficient. Remarkably, a short histidine-rich domain (HRD), which is derived from the internal disordered region (IDR) in the human CYCT1, a protein capable of liquid-liquid phase separation (LLPS), enhanced V1 editing at on-targets as well as off-targets, the latter effect being minor. The V1-HRD fusion protein formed puncta characteristic of LLPS, and various other IDRs (but not an LLPS-impaired mutant) could replace HRD to effectively induce puncta and potentiate V1, suggesting that the diverse domains acted via a common, LLPS-based mechanism. Importantly, the HRD fusion strategy was applicable to various other types of C > U RNA editors. Our study expands the RNA editing toolbox and showcases a general method for stimulating C > U RNA base editors.","journal":"Molecular Therapy — Nucleic Acids","year":2024,"id":483250,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"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":1324141,"name":"Junjun Lv","orcid":"0000-0001-6557-0846","position":1,"is_corresponding":false},{"id":422494,"name":"Wei Ge","orcid":"0000-0002-9907-512X","position":2,"is_corresponding":false},{"id":1324450,"name":"Yijie Yang","orcid":null,"position":3,"is_corresponding":false},{"id":1324451,"name":"Kunlun Yan","orcid":null,"position":4,"is_corresponding":false},{"id":640663,"name":"Jianguo Wu","orcid":"0000-0002-8326-2895","position":5,"is_corresponding":false},{"id":1324452,"name":"Jianyang Ge","orcid":null,"position":6,"is_corresponding":false},{"id":578330,"name":"Simone Rauch","orcid":"0000-0003-1511-269X","position":7,"is_corresponding":false},{"id":551852,"name":"Bryan C. Dickinson","orcid":"0000-0002-9616-1911","position":8,"is_corresponding":false},{"id":1324142,"name":"Tian Chi","orcid":"0000-0002-9675-6990","position":9,"is_corresponding":false},{"id":1324140,"name":"Minghui Di","orcid":"0000-0001-7364-8578","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T02:07:22.248464Z","pmid":"38721279","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":[]}