The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Binary specification of nonsense codons by splicing and cytoplasmic translation
Open accessAbstract
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.
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“The frameshift mutation leads to an ~90% reduction in cfap20 transcript abundance (Fig. 2c), presumably due to nonsense-mediated decay24–26.”
From The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision (2022) · cites this paper as [26]
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Metadata
- Authors
- Thermann, R., Neu‐Yilik, G., Deters, A., Frede, U., Wehr, K., Hagemeier, C., Hentze, M. W., & Kulozik, A. E.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Hentze, Matthias W.
- Kulozik, Andreas E.
- Venue
- The EMBO Journal
- Published
- 1998-06-15
- Volume
- 17
- Issue
- 12
- Pages
- 3484-3494
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170685
- OpenAlex
- W2036625038
- Cited by
- 406
- References
- 59
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 3 · 2023: 12 · 2022: 15 · 2021: 17 · 2020: 15 · 2019: 14 · 2018: 15 · 2017: 12 · 2016: 15 · 2015: 15 · 2014: 8 · 2013: 19 · 2012: 8
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Chinese Academy of Agricultural Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Keywords
- nonsense-mediated mRNA decay, stop codon, premature stop codon, beta-globin mRNA, beta-thalassemia, splicing, splice junctions, cytoplasmic translation, mRNA degradation, frameshift mutation
- MeSH terms
- HeLa Cells, Humans, RNA, Messenger, Protein Biosynthesis, Codon, Terminator, Codon, Nonsense, Fluorescent Antibody Technique, Indirect
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