{"doi":"10.1016/j.mocell.2025.100250","title":"N-Terminal deleted isoforms of E3 ligase RNF220 are ubiquitously expressed and required for mouse muscle differentiation","abstract":"Four isoform peptides of the novel E3 ligase ring finger protein 220 (RNF220) have been identified in humans. However, all of the previous studies have predominantly focused on isoform 1 (the full-length form), which consists of 566 amino acids. Here, we show that a shorter isoform, which is 308 amino acids lacking most of the N-terminus (human isoform 4; mouse isoform 3; ΔN-RNF220), is the predominant and ubiquitously expressed variant that warrants functional investigation. Both isoform 1 and ΔN-RNF220 are expressed in the brain; however, ΔN-RNF220 is the major isoform expressed in all other tissues in mice. Consistently, H3K4me3 ChIP-seq data from ENCODE reveal that the transcription start site for ΔN-RNF220 demonstrates broader and stronger activity across human tissues than that of isoform 1. ΔN-RNF220 produces 2 peptides (4a and 4b) through alternative translation initiation, with isoform 4b displaying distinct subcellular localization, subnuclear structures and interaction with a nuclear protein WDR5. Notably, during embryonic stem cell differentiation into neural stem cells, isoform 1 expression increases, whereas ΔN-RNF220 expression decreases. In murine myoblasts, ΔN-RNF220 is the sole expressed isoform and is required for MyoD and myogenin expression, as well as for muscle differentiation. Our findings highlight ΔN-RNF220 as the ubiquitously and highly expressed variant, likely playing a fundamental role across tissues while exhibiting functional differences from isoform 1. These results emphasize the critical importance of ΔN-RNF220 in future studies investigating the biological functions of RNF220.","journal":"Molecules and Cells","year":2025,"id":528430,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1406772,"name":"Sojung Ha","orcid":null,"position":1,"is_corresponding":false},{"id":141951,"name":"Donald Wolfgeher","orcid":"0000-0002-8960-338X","position":2,"is_corresponding":false},{"id":89248,"name":"Jeewon Kim","orcid":"0000-0002-1063-0239","position":3,"is_corresponding":false},{"id":1406364,"name":"Young-Hyun Go","orcid":"0000-0001-8915-1451","position":4,"is_corresponding":false},{"id":1406365,"name":"Hyuk‐Jin Cha","orcid":"0000-0001-9277-2662","position":5,"is_corresponding":false},{"id":295068,"name":"Gyu‐Un Bae","orcid":"0000-0003-4625-4957","position":6,"is_corresponding":false},{"id":141953,"name":"Stephen J. Kron","orcid":"0000-0003-1518-2436","position":7,"is_corresponding":false},{"id":1406366,"name":"Woo-Young Kim","orcid":"0000-0002-2895-4995","position":8,"is_corresponding":false},{"id":1406771,"name":"SeokGyeong Choi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:50:48.492873Z","pmid":"40609864","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":[]}