{"doi":"10.1101/2024.11.05.622011","title":"Nascent transcript O-MAP reveals the molecular architecture of a single-locus subnuclear compartment built by RBM20 and the <i>TTN</i> RNA","abstract":"ABSTRACT Eukaryotic nuclei adopt a highly compartmentalized architecture that influences nearly all genomic processes. Understanding how this architecture impacts gene expression has been hindered by a lack of tools for elucidating the molecular interactions at individual genomic loci. Here, we adapt oligonucleotide-mediated proximity-interactome mapping (O-MAP) to biochemically characterize discrete, micron-scale nuclear neighborhoods. By targeting O-MAP to introns within the TTN pre-mRNA, we systematically map the chromatin loci, RNAs, and proteins within a muscle-specific RNA factory organized around the TTN locus. This reveals an unanticipated compartmental architecture that organizes cis - and trans -interacting chromosomal domains, including a hub of transcriptionally silenced chromatin. The factory also recruits dozens of unique RNA-binding and chromatin-scaffolding factors, including QKI and SAFB, along with their target transcripts. Loss of the cardiac-specific splicing factor RBM20—a master regulator of TTN splicing that is mutated in dilated cardiomyopathy—remodels nearly every facet of this architecture. This establishes O-MAP as a pioneering method for probing single-locus, microcompartment-level interactions that are opaque to conventional tools. Our findings suggest new mechanisms by which coding genes can \"moonlight\" in nuclear-architectural roles.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485291,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9488,"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":651017,"name":"Aidan M. Fenix","orcid":"0000-0002-1564-7347","position":1,"is_corresponding":false},{"id":1173211,"name":"Daphnée M. Marciniak","orcid":"0009-0002-4830-8365","position":2,"is_corresponding":false},{"id":1181329,"name":"Qiaoyi Lin","orcid":null,"position":3,"is_corresponding":false},{"id":1328339,"name":"Sara Bianchi","orcid":null,"position":4,"is_corresponding":false},{"id":490540,"name":"Borislav H. Hristov","orcid":"0000-0002-1414-8378","position":5,"is_corresponding":false},{"id":1327861,"name":"Shuai Li","orcid":"0000-0002-0590-2199","position":6,"is_corresponding":false},{"id":557048,"name":"Conor K. Camplisson","orcid":"0000-0001-5085-7924","position":7,"is_corresponding":false},{"id":1209981,"name":"Rose Fields","orcid":"0009-0006-3365-4598","position":8,"is_corresponding":false},{"id":21366,"name":"Brian J. Beliveau","orcid":"0000-0003-1314-3118","position":9,"is_corresponding":false},{"id":107035,"name":"Devin K. Schweppe","orcid":"0000-0002-3241-6276","position":10,"is_corresponding":false},{"id":4958,"name":"William Stafford Noble","orcid":"0000-0001-7283-4715","position":11,"is_corresponding":false},{"id":31807,"name":"Shao‐En Ong","orcid":"0000-0003-3314-5903","position":12,"is_corresponding":false},{"id":548421,"name":"Alessandro Bertero","orcid":"0000-0002-4919-9087","position":13,"is_corresponding":false},{"id":366668,"name":"Charles E. Murry","orcid":"0000-0003-3862-6773","position":14,"is_corresponding":false},{"id":1209982,"name":"David M Shechner","orcid":"0000-0002-0574-256X","position":15,"is_corresponding":false},{"id":1209979,"name":"Evan E. Kania","orcid":"0000-0002-0266-6610","position":0,"is_corresponding":true}],"reference_count":107,"raw_metadata":null,"created_at":"2026-07-19T02:07:47.633574Z","pmid":"39574693","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":[]}