ArticleProceedings of the National Academy of Sciences of the United States of America2013
Inhibition of SMG-8, a subunit of SMG-1 kinase, ameliorates nonsense-mediated mRNA decay-exacerbated mutant phenotypes without cytotoxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Suppressor with morphogenetic effect on genitalia 7 (SMG7) drives hepatocellular carcinoma progression through context-dependent nonsense-mediated decay (NMD) dysregulation.Molecular biomedicine · 2026Article
- Two stress-responsive kinases suppress ferroptosis by activating antioxidant programs under mild oxidative stress.Signal transduction and targeted therapy · 2026Article
- Identification of small molecules that enhance aminoglycoside-mediated suppression ofMolecular therapy. Oncology · 2026Article
- PCOS combined with obesity aggravates the metabolic and immune abnormality in females.BMC women's health · 2026Article
- Variable efficiency of nonsense-mediated mRNA decay across human tissues, tumors and individuals.Genome biology · 2025Article
- An adapted MS2-MCP system to visualize endogenous cytoplasmic mRNA with live imaging in Caenorhabditis elegans.PLoS biology · 2024Article
- Nonsense-mediated RNA decay: an emerging modulator of malignancy.Nature reviews. Cancer · 2022Review
- Gene-specific nonsense-mediated mRNA decay targeting for cystic fibrosis therapy.Nature communications · 2022Article
- CFTR mRNAs with nonsense codons are degraded by the SMG6-mediated endonucleolytic decay pathway.Nature communications · 2022Article
- Therapeutic promise of engineered nonsense suppressor tRNAs.Wiley interdisciplinary reviews. RNA · 2021Review
- Nonsense suppression therapies in human genetic diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Nonsense Suppression Therapy: New Hypothesis for the Treatment of Inherited Bone Marrow Failure Syndromes.International journal of molecular sciences · 2020Review
- The impact of nonsense-mediated mRNA decay on genetic disease, gene editing and cancer immunotherapy.Nature genetics · 2019Article
- Disruption of cardiac thin filament assembly arising from a mutation inScience advances · 2019Article
- Environmental stresses suppress nonsense-mediated mRNA decay (NMD) and affect cells by stabilizing NMD-targeted gene expression.Scientific reports · 2019Article
- Antisense suppression of the nonsense mediated decay factor Upf3b as a potential treatment for diseases caused by nonsense mutations.Genome biology · 2018Article
- Endoplasmic reticulum stress preconditioning modifies intracellular mercury content by upregulating membrane transporters.Scientific reports · 2017Article
- Structure of a SMG8-SMG9 complex identifies a G-domain heterodimer in the NMD effector proteins.RNA (New York, N.Y.) · 2017Article
- Fluorescence Amplification Method for Forward Genetic Discovery of Factors in Human mRNA Degradation.Molecular cell · 2017Article
- NMD Classifier: A reliable and systematic classification tool for nonsense-mediated decay events.PloS one · 2017Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that eliminates aberrant mRNAs containing premature termination codons (PTCs). NMD inhibits the production of aberrant proteins that still retain, at least in part, wild-type function as well as dominant-negative peptides. Therefore, the selective inhibition of NMD has the potential to ameliorate NMD-exacerbated mutant phenotypes. However, we do not have sufficient knowledge of how to effectively suppress NMD with minimum cytotoxic effects. In this study, we aimed to identify NMD-related factors that can be targeted to efficiently inhibit NMD without causing significant cytotoxicity to restore the levels of truncated but partially functional proteins. We evaluated the knockdown of 15 NMD components in Ullrich congenital muscular dystrophy fibroblasts, which have a homozygous frameshift mutation causing a PTC in the collagen type VI α 2 gene. Of the 15 NMD factors tested, knockdown of SMG-8 produced the best effect for restoring defective mRNA and protein levels without affecting cell growth, cell-cycle progression, or endoplasmic reticulum stress. The efficacy of SMG-8 knockdown to improve the mutant phenotype was confirmed using another cell line, from a cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy patient who carries a PTC-containing mutation in HtrA serine peptidase 1. Our results suggest that SMG-8 is an appropriate target for inhibiting NMD to improve NMD-exacerbated mutant phenotypes. NMD inhibition by knockdown of SMG-8 may also be useful to induce synergy in combining the use of read-through drugs for patients with nonsense mutation-associated diseases.
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