{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Choi S"],"funding":["Korea Ministry of Education","Ministry of Education, Ethiopia","Korea Health Industry Development Institute","Korea Ministry of Science and ICT","National Institutes of Health","National Research Foundation of Korea"],"pagination":["100250"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12296455"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["48(9)"],"pubmed_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"],"pubmed_title":["N-Terminal deleted isoforms of E3 ligase RNF220 are ubiquitously expressed and required for mouse muscle differentiation."],"pmcid":["PMC12296455"],"funding_grant_id":["2020R1A2C1006091","R01s AG069865","CA254047","RS-2024-00509503","RS-2024-00463034","RS-2022-NR070845","HI21C2509"],"pubmed_authors":["Choi S","Wolfgeher DJ","Kim WY","Kim JW","Kron SJ","Go YH","Cha HJ","Bae GU","Ha S"],"additional_accession":[]},"is_claimable":false,"name":"N-Terminal deleted isoforms of E3 ligase RNF220 are ubiquitously expressed and required for mouse muscle differentiation.","description":"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.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-07-02T03:22:02.278Z","creation":"2025-08-28T03:04:46.352Z"},"accession":"S-EPMC12296455","cross_references":{"pubmed":["40609864"],"doi":["10.1016/j.mocell.2025.100250"]}}