{"doi":"10.1371/journal.pbio.3002317","title":"The transcription factor DUX4 orchestrates translational reprogramming by broadly suppressing translation efficiency and promoting expression of DUX4-induced mRNAs","abstract":"Translational control is critical for cell fate transitions during development, lineage specification, and tumorigenesis. Here, we show that the transcription factor double homeobox protein 4 (DUX4), and its previously characterized transcriptional program, broadly regulates translation to change the cellular proteome. DUX4 is a key regulator of zygotic genome activation in human embryos, whereas misexpression of DUX4 causes facioscapulohumeral muscular dystrophy (FSHD) and is associated with MHC-I suppression and immune evasion in cancer. We report that translation initiation and elongation factors are disrupted downstream of DUX4 expression in human myoblasts. Genome-wide translation profiling identified mRNAs susceptible to DUX4-induced translation inhibition, including those encoding antigen presentation factors and muscle lineage proteins, while DUX4-induced mRNAs were robustly translated. Endogenous expression of DUX4 in human FSHD myotubes and cancer cell lines also correlated with reduced protein synthesis and MHC-I presentation. Our findings reveal that DUX4 orchestrates cell state conversion by suppressing the cellular proteome while maintaining translation of DUX4-induced mRNAs to promote an early developmental program.","journal":"PLoS Biology","year":2023,"id":358722,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9461,"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":587974,"name":"Ellen Paatela","orcid":"0000-0002-7291-0850","position":1,"is_corresponding":false},{"id":993137,"name":"Sean Bennett","orcid":"0000-0002-3081-0536","position":2,"is_corresponding":false},{"id":296634,"name":"Chao-Jen Wong","orcid":null,"position":3,"is_corresponding":false},{"id":294718,"name":"Amy E. Campbell","orcid":"0000-0001-6513-5836","position":4,"is_corresponding":false},{"id":647342,"name":"Cynthia L. Wladyka","orcid":null,"position":5,"is_corresponding":false},{"id":1050701,"name":"Andrew A. Smith","orcid":"0000-0003-1307-4677","position":6,"is_corresponding":false},{"id":667918,"name":"Sujatha Jagannathan","orcid":"0000-0001-9039-2631","position":7,"is_corresponding":false},{"id":362115,"name":"Andrew C. Hsieh","orcid":"0000-0002-0897-1050","position":8,"is_corresponding":false},{"id":294722,"name":"Stephen J. Tapscott","orcid":"0000-0002-0319-0968","position":9,"is_corresponding":false},{"id":681667,"name":"Danielle C. Hamm","orcid":"0000-0003-2966-7389","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-19T01:13:48.379546Z","pmid":"37747887","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":[]}