ArticleCell reports2023
Compromised nonsense-mediated RNA decay results in truncated RNA-binding protein production upon DUX4 expression.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- FSHD muscle shows perturbation in fibroadipogenic progenitor cells, mitochondrial function and alternative splicing independently of inflammation.Human molecular genetics · 2024Pooled it
- Identification and characterisation of a novel homozygous KDM5A variant associated with severe axial hypotonia, seizures, and cardiac anomalies.Journal of human genetics · 2026Article
- DUX4-induced HSATII RNA accumulation drives protein aggregation, impacting RNA processing pathways.The Journal of cell biology · 2026Article
- Genomic stop codon scanning reveals quantitative principles of nonsense-mediated mRNA decay.bioRxiv : the preprint server for biology · 2025Article
- Article
- AAV-shDUX4 provides short-term benefits but limited long-term efficacy in a DUX4 mouse model of FSHD.Molecular therapy. Methods & clinical development · 2025Article
- Coordinated expression of retained introns and poison exons in renal cell carcinoma.Cell reports · 2025Article
- The recent clinical trial of losmapimod for the treatment of facioscapulohumeral muscular dystrophy.Neuromuscular disorders : NMD · 2025Review
- IncreasedInternational journal of molecular sciences · 2025Article
- DUX4 activates common and context-specific intergenic transcripts and isoforms.Science advances · 2025Article
- Facioscapulohumeral Dystrophy: Molecular Basis and Therapeutic Opportunities.Cold Spring Harbor perspectives in biology · 2025Review
- Therapeutic targeting of RNA for neurological and neuromuscular disease.Genes & development · 2024Review
- The Art of Finding the Right Drug Target: Emerging Methods and Strategies.Pharmacological reviews · 2024Review
- Systemic Pharmacotherapeutic Treatment of the ACTA1-MCM/FLExDUX4 Preclinical Mouse Model of FSHD.International journal of molecular sciences · 2024Article
- Muscle eosinophilia is a hallmark of chronic disease in facioscapulohumeral muscular dystrophy.Human molecular genetics · 2024Article
- The DUX4-HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected.International journal of molecular sciences · 2024Article
- Apabetalone, a Clinical-Stage, Selective BET Inhibitor, Opposes DUX4 Target Gene Expression in Primary Human FSHD Muscle Cells.Biomedicines · 2023Article
- The transcription factor DUX4 orchestrates translational reprogramming by broadly suppressing translation efficiency and promoting expression of DUX4-induced mRNAs.PLoS biology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Nonsense-mediated RNA decay (NMD) degrades transcripts carrying premature termination codons. NMD is thought to prevent the synthesis of toxic truncated proteins. However, whether loss of NMD results in widespread production of truncated proteins is unclear. A human genetic disease, facioscapulohumeral muscular dystrophy (FSHD), features acute inhibition of NMD upon expression of the disease-causing transcription factor, DUX4. Using a cell-based model of FSHD, we show production of truncated proteins from physiological NMD targets and find that RNA-binding proteins are enriched for aberrant truncations. The NMD isoform of one RNA-binding protein, SRSF3, is translated to produce a stable truncated protein, which is detected in FSHD patient-derived myotubes. Ectopic expression of truncated SRSF3 confers toxicity, and its downregulation is cytoprotective. Our results delineate the genome-scale impact of NMD loss. This widespread production of potentially deleterious truncated proteins has implications for FSHD biology as well as other genetic diseases where NMD is therapeutically modulated.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.