Binary specification of nonsense codons by splicing and cytoplasmic translation
| Autor: | Matthias W. Hentze, Andrea Deters, Kristina Wehr, Christian Hagemeier, Gabriele Neu-Yilik, Andreas E. Kulozik, Ute Frede, Rolf Thermann |
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| Rok vydání: | 1998 |
| Předmět: |
Silent mutation
Genetics General Immunology and Microbiology General Neuroscience Cytoplasmic translation Nonsense mutation Nonsense-mediated decay Biology General Biochemistry Genetics and Molecular Biology Stop codon Open reading frame Codon Nonsense Protein Biosynthesis Codon usage bias Codon Terminator Humans Exon junction complex RNA Messenger Fluorescent Antibody Technique Indirect Molecular Biology HeLa Cells Research Article |
| Zdroj: | The EMBO Journal. 17:3484-3494 |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/17.12.3484 |
| Popis: | Premature translation termination codons resulting from nonsense or frameshift mutations are common causes of genetic disorders. Complications arising from the synthesis of C-terminally truncated polypeptides can be avoided by 'nonsense-mediated decay' of the mutant mRNAs. Premature termination codons in the beta-globin mRNA cause the common recessive form of beta-thalassemia when the affected mRNA is degraded, but the more severe dominant form when the mRNA escapes nonsense-mediated decay. We demonstrate that cells distinguish a premature termination codon within the beta-globin mRNA from the physiological translation termination codon by a two-step specification mechanism. According to the binary specification model proposed here, the positions of splice junctions are first tagged during splicing in the nucleus, defining a stop codon operationally as a premature termination codon by the presence of a 3' splicing tag. In the second step, cytoplasmic translation is required to validate the 3' splicing tag for decay of the mRNA. This model explains nonsense-mediated decay on the basis of conventional molecular mechanisms and allows us to propose a common principle for nonsense-mediated decay from yeast to man. |
| Databáze: | OpenAIRE |
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