{"doi":"10.1126/science.adh0059","title":"Structural basis for inactivation of PRC2 by G-quadruplex RNA","abstract":"Polycomb repressive complex 2 (PRC2) silences genes through trimethylation of histone H3K27. PRC2 associates with numerous precursor messenger RNAs (pre-mRNAs) and long noncoding RNAs (lncRNAs) with a binding preference for G-quadruplex RNA. In this work, we present a 3.3-Å-resolution cryo-electron microscopy structure of PRC2 bound to a G-quadruplex RNA. Notably, RNA mediates the dimerization of PRC2 by binding both protomers and inducing a protein interface composed of two copies of the catalytic subunit EZH2, thereby blocking nucleosome DNA interaction and histone H3 tail accessibility. Furthermore, an RNA-binding loop of EZH2 facilitates the handoff between RNA and DNA, another activity implicated in PRC2 regulation by RNA. We identified a gain-of-function mutation in this loop that activates PRC2 in zebrafish. Our results reveal mechanisms for RNA-mediated regulation of a chromatin-modifying enzyme.","journal":"Science","year":2023,"id":318157,"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":68,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":256664,"name":"Anne R. Gooding","orcid":"0000-0002-5367-0038","position":1,"is_corresponding":false},{"id":651190,"name":"Wayne O. Hemphill","orcid":"0000-0002-8136-1574","position":2,"is_corresponding":false},{"id":1025171,"name":"Brittney Love","orcid":"0000-0002-3746-2829","position":3,"is_corresponding":false},{"id":503535,"name":"Anne L. Robertson","orcid":"0000-0002-8526-9433","position":4,"is_corresponding":false},{"id":575690,"name":"Liqi Yao","orcid":"0000-0001-8344-6531","position":5,"is_corresponding":false},{"id":49576,"name":"Leonard I. Zon","orcid":"0000-0003-0860-926X","position":6,"is_corresponding":false},{"id":270302,"name":"Trista E. North","orcid":"0000-0003-1249-563X","position":7,"is_corresponding":false},{"id":778336,"name":"Vignesh Kasinath","orcid":"0000-0003-2686-0546","position":8,"is_corresponding":false},{"id":256666,"name":"Thomas R. Cech","orcid":"0000-0001-7338-3389","position":9,"is_corresponding":false},{"id":382918,"name":"Jiarui Song","orcid":"0000-0003-1376-1389","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T01:07:01.300821Z","pmid":"37733873","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":[]}