{"doi":"10.3390/cells14231912","title":"Alternative Splicing (AS) Provides an Alternative Mechanism for Regulating GLIS3 Expression and Activity","abstract":"The Krüppel-like transcription factor GLIS3 plays an important regulatory role in the development of various tissues, both in mice and humans. Loss-of-function mutations in GLIS3 are implicated in several pathologies, including polycystic kidney disease, diabetes, and hypothyroidism. Previous studies have reported that the mouse Glis3 gene generates a 7524 bp mRNA encoding a 935 amino acid (aa) protein, with a homologous human protein of 930 aa. Here, we identify a shorter mouse mRNA lacking the third exon, producing a shorter 659 aa GLIS3 protein. This shorter transcript is expressed at a higher level than the longer transcript in all mouse tissues tested and produces a protein that is more stable and exhibits a greater transactivation potential. This suggests that the 276 aa N-terminus in the longer mouse GLIS3 protein encompasses important regulatory domain(s). Mass spectrometry identified several phosphorylation sites that may contribute to the post-translational regulation of GLIS3 activity and function and several known members of co-activator and co-repressor complexes, consistent with the concept that GLIS3 can act both as a transcriptional repressor and activator. These data offer important insights into how GLIS3 activity is regulated and offer potential mechanisms for its control during tissue development and disease.","journal":"Cells","year":2025,"id":583878,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"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":247168,"name":"Sara A. Grimm","orcid":"0000-0003-3050-1909","position":1,"is_corresponding":false},{"id":44758,"name":"Jason Williams","orcid":"0000-0002-3804-2594","position":2,"is_corresponding":false},{"id":97236,"name":"Anton M. Jetten","orcid":"0000-0003-0954-4445","position":3,"is_corresponding":false},{"id":349040,"name":"David W. Scoville","orcid":"0000-0003-3748-6502","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:59:07.970345Z","pmid":"41369402","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":[]}