ArticleNucleic acids research1995
Nuclear degradation of nonsense mutated beta-globin mRNA: a post-transcriptional mechanism to protect heterozygotes from severe clinical manifestations of beta-thalassemia?
Article in Nucleic acids research, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 71 citations in OpenAlex.
- Technologies for Targeted RNA Degradation and Induced RNA Decay.Chemical reviews · 2024Review
- Nonsense-mediated mRNA decay pathway in plants under stress: general gene regulatory mechanism and advances.Planta · 2024Review
- Coupled protein quality control during nonsense-mediated mRNA decay.Journal of cell science · 2023Article
- Inhibition of Nonsense-Mediated Decay Induces Nociceptive Sensitization through Activation of the Integrated Stress Response.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Nonsense suppression therapies in human genetic diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Ribosome Recycling by ABCE1 Links Lysosomal Function and Iron Homeostasis to 3' UTR-Directed Regulation and Nonsense-Mediated Decay.Cell reports · 2020Article
- Quality and quantity control of gene expression by nonsense-mediated mRNA decay.Nature reviews. Molecular cell biology · 2019Review
- Small RNA expression from the human macrosatellite DXZ4.G3 (Bethesda, Md.) · 2014Article
- The dharma of nonsense-mediated mRNA decay in mammalian cells.Molecules and cells · 2014Review
- Organizing principles of mammalian nonsense-mediated mRNA decay.Annual review of genetics · 2013Review
- When a ribosome encounters a premature termination codon.BMB reports · 2013Review
- Unspliced precursors of NMD-sensitive β-globin transcripts exhibit decreased steady-state levels in erythroid cells.PloS one · 2012Article
- RNA decay and RNA silencing in plants: competition or collaboration?Frontiers in plant science · 2011Article
- Premature termination codons do not affect the rate of splicing of neighboring introns.RNA (New York, N.Y.) · 2004Article
- Nonsense-containing mRNAs that accumulate in the absence of a functional nonsense-mediated mRNA decay pathway are destabilized rapidly upon its restitution.Molecular and cellular biology · 2003Article
- T-cell receptor sequences that elicit strong down-regulation of premature termination codon-bearing transcripts.The EMBO journal · 2002Article
- Nonsense-mediated decay of human HEXA mRNA.Molecular and cellular biology · 2001Article
- Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes.Molecular and cellular biology · 2000Article
- A mutated human homologue to yeast Upf1 protein has a dominant-negative effect on the decay of nonsense-containing mRNAs in mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- Intron function in the nonsense-mediated decay of beta-globin mRNA: indications that pre-mRNA splicing in the nucleus can influence mRNA translation in the cytoplasm.RNA (New York, N.Y.) · 1998Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonsense mutations of the beta-globin gene are a common cause of beta-thalassemia. It is a hallmark of these mutations not only to cause a lack of protein synthesis but also a reduction of mRNA expression. Both the pathophysiologic significance and the underlying mechanisms for this surprising phenomenon have so far remained enigmatic. We report that the reduction of the fully spliced mutant beta-globin mRNA already manifests itself within the nucleus. In contrast, the levels of mutant pre-mRNA are normal. The promoter and the 5'-untranslated region (5'-UTR) of the herpes simplex virus type 1 thymidine kinase (HSV1 Tk) gene can independently circumvent this recognition/response mechanism in cis and restore nonsense mutated beta-globin mRNA expression to normal levels. These two genetic elements can thus exert a dominant influence on the post-transcriptional control of nonsense mutated beta-globin gene expression. While wild-type mRNA levels are restored by fusion of the HSV1 Tk 5'-UTR to the nonsense mutated beta-globin reading frame, translation of a wildtype reading frame in such a hybrid is precluded. In contrast, the HSV1 Tk promoter appears to efficiently deliver the mRNA to the translational apparatus. The 5'-UTR and the promoter sequences therefore control the nuclear fate of nonsense mutated beta-globin mRNA by separable pathways. The nuclear mRNA degradation mechanisms examined here may prevent the synthesis of C-terminally truncated beta-globin chain fragments and may protect heterozygotes from clinically relevant symptoms of beta-thalassemia.
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