ArticlePLoS biology2023
The transcription factor DUX4 orchestrates translational reprogramming by broadly suppressing translation efficiency and promoting expression of DUX4-induced mRNAs.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- DUX4-induced HSATII RNA accumulation drives protein aggregation, impacting RNA processing pathways.The Journal of cell biology · 2026Article
- Review
- Proteomics-based characterization of ribosome heterogeneity in adult mouse organs.Cellular and molecular life sciences : CMLS · 2025Article
- Facioscapulohumeral Dystrophy: Molecular Basis and Therapeutic Opportunities.Cold Spring Harbor perspectives in biology · 2025Review
- Glucose binds and activates NSUN2 to promote translation and epidermal differentiation.Nucleic acids research · 2024Article
- The DUX4-HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected.International journal of molecular sciences · 2024Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
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.
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Registered trials
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