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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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Cites
Kozak, M. (1986) · Cell · doi:10.1016/0092-8674(86)90762-2 · Cited by 4,741
Hentze, M. W., & Kühn, L. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8175 · Cited by 1,292
Self-citationRegulating the fate of mRNA: the control of cellular iron metabolism
Klausner, R. D., Rouault, T. A., & Harford, J. B. (1993) · Cell · doi:10.1016/0092-8674(93)90046-s · Cited by 1,210
A versatilein vivoandin vitroeukaryotic expression vector for protein engineering
Green, S., Issemann, I., & Sheer, E. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.1.369 · Cited by 659
When cells stop making sense: effects of nonsense codons on RNA metabolism in vertebrate cells.
Maquat, L. E. (1995) · Europe PMC (PubMed Central) · Cited by 509
mRNA surveillance by the Caenorhabditis elegans smg genes.Preprint
Pulak, R., & Anderson, P. (1993) · Genes & Development · doi:10.1101/gad.7.10.1885 · Cited by 483
The Skipping of Constitutive Exons in Vivo Induced by Nonsense Mutations
Dietz, H. C., Valle, D., Francomano, C. A., Kendzior, R. J., Pyeritz, R. E., & Cutting, G. A. (1993) · Science · doi:10.1126/science.8430317 · Cited by 417
Nonsense Mutations in the Dihydrofolate Reductase Gene Affect RNA Processing
Urlaub, G., Mitchell, P. J., Ciudad, C. J., & Chasin, L. A. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.7.2868 · Cited by 358
Carter, M. S., Doskow, J., Morris, P., Li, S., Nhim, R. P., Sandstedt, S. A., & Wilkinson, M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.48.28995 · Cited by 330
Translational termination efficiency in mammals is influenced by the base following the stop codon
McCaughan, K. K., Brown, C. M., Dalphin, M. E., Berry, M. J., & Tate, W. P. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5431 · Cited by 284
A splicing‐dependent regulatory mechanism that detects translation signals.
Carter, M. S., Li, S., & Wilkinson, M. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00983.x · Cited by 282
Gray, N. K., & Hentze, M. W. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06699.x · Cited by 276
Self-citationUnstable β-globin mRNA in mRNA-deficient β0 thalassemia
Maquat, L. E., Kinniburgh, A. J., Rachmilewitz, E. A., & Ross, J. (1981) · Cell · doi:10.1016/0092-8674(81)90396-2 · Cited by 271
Hentze, M. W., Rouault, T. A., Caughman, S. W., Dancis, A., Harford, J. B., & Klausner, R. D. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.19.6730 · Cited by 249
Self-citationNonsense mutations in the human beta-globin gene affect mRNA metabolism.
Baserga, S. J., & Benz, E. J. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.7.2056 · Cited by 235
Visa, N., Izaurralde, E., Ferreira, J. A., Daneholt, B., & Mattaj, I. W. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.133.1.5 · Cited by 232
Pantopoulos, K., & Hentze, M. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.5.1267 · Cited by 220
Self-citationPremature Translation Termination Mediates Triosephosphate Isomerase mRNA Degradation
Daar, I. O., & Maquat, L. E. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.2.802 · Cited by 217
Cheng, J., & Maquat, L. E. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.3.1892 · Cited by 205
Zillmann, M., Zapp, M. L., & Berget, S. M. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.2.814 · Cited by 191
Consequences of frameshift mutations at the immunoglobulin heavy chain locus of the mouse.
Baumann, B., Potash, M. J., & Köhler, G. (1985) · The EMBO Journal · doi:10.1002/j.1460-2075.1985.tb03636.x · Cited by 186
Molecular basis for dominantly inherited inclusion body beta-thalassemia.
Thein, S. L., Hesketh, C., Taylor, P., Temperley, I. J., Hutchinson, R. M., Old, J. M., Wood, W. G., Clegg, J. B., & Weatherall, D. J. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.10.3924 · Cited by 185
Evidence that translation reinitiation abrogates nonsense‐mediated mRNA decay in mammalian cells
Zhang, J., & Maquat, L. E. (1997) · The EMBO Journal · doi:10.1093/emboj/16.4.826 · Cited by 184
Belgrader, P., Cheng, J., & Maquat, L. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.2.482 · Cited by 182
Introns are cis Effectors of the Nonsense-Codon-Mediated Reduction in Nuclear mRNA Abundance
Cheng, J., Belgrader, P., Zhou, X., & Maquat, L. E. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.9.6317-6325.1994 · Cited by 159
Applequist, S. E., Selg, M., Raman, C., & Jäck, H. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.4.814 · Cited by 157
Cheng, J., Fogel‐Petrovic, M., & Maquat, L. E. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.10.5215 · Cited by 157
Goossen, B., & Hentze, M. W. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.5.1959-1966.1992 · Cited by 145
Self-citationMaintenance of an open reading frame as an additional level of scrutiny during splice site selection
Dietz, H. C., & Kendzior, R. J. (1994) · Nature Genetics · doi:10.1038/ng1094-183 · Cited by 140
Mammalian nonsense codons can be cis effectors of nuclear mRNA half-life.
Belgrader, P., Cheng, J., Zhou, X., Stephenson, L. S., & Maquat, L. E. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8219 · Cited by 136
Aoufouchi, S., Yélamos, J., & Milstein, C. (1996) · Cell · doi:10.1016/s0092-8674(00)81119-8 · Cited by 132
In Vitro Recombination and Mutagenesis by Overlap Extension PCR
Pogulis, R. J., Vallejo, A. N., & Pease, L. R. (2003) · Humana Press eBooks · doi:10.1385/0-89603-332-5:167 · Cited by 128
Belgrader, P., & Maquat, L. E. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.9.6326 · Cited by 128
Ruiz-Echevarría, M. J., González, C. I., & Peltz, S. W. (1998) · The EMBO Journal · doi:10.1093/emboj/17.2.575 · Cited by 126
Naeger, L. K., Schoborg, R. V., Zhao, Q., Tullis, G. E., & Pintel, D. J. (1992) · Genes & Development · doi:10.1101/gad.6.6.1107 · Cited by 124
Baserga, S. J., & Benz, E. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.7.2935 · Cited by 122
A model for the structure and functions of iron-responsive elements
Hentze, M. W., Caughman, S. W., Casey, J. L., Kodier, D. M., Rouault, T. A., Harford, J. B., & Klausner, R. D. (1988) · Gene · doi:10.1016/0378-1119(88)90145-x · Cited by 116
Self-citationNonsense Codons in Human β-Globin mRNA Result in the Production of mRNA Degradation Products
Lim, S. K., Sigmund, C. D., Gross, K. W., & Maquat, L. E. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.3.1149-1161.1992 · Cited by 114
Humphries, R. K., Ley, T. J., Anagnou, N., Baur, A., & Nienhuis, A. (1984) · Blood · doi:10.1182/blood.v64.1.23.bloodjournal64123 · Cited by 107
Kessler, O., Jiang, Y., & Chasin, L. A. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.10.6211 · Cited by 105
Making sense of nonsense in yeast
Ruiz-Echevarría, M. J., Czaplinski, K., & Peltz, S. W. (1996) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)10055-4 · Cited by 98
Zillmann, M., Zapp, M. L., & Berget, S. M. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.2.814-821.1988 · Cited by 95
Lozano, F., Maertzdorf, B., Pannell, R., & Milstein, C. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06783.x · Cited by 94
Takeshita, K., Forget, B. G., Scarpa, A. L., & Benz, E. J. (1984) · Blood · doi:10.1182/blood.v64.1.13.13 · Cited by 93
Premature Translation Termination Mediates Triosephosphate Isomerase mRNA Degradation
Daar, I. O., & Maquat, L. E. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.2.802-813.1988 · Cited by 84
Lim, S. K., & Maquat, L. E. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05405.x · Cited by 83
Li, S., Leonard, D., & Wilkinson, M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.6.985 · Cited by 75
Differential regulation of two related RNA-binding proteins, iron regulatory protein (IRP) and IRPB.
Pantopoulos, K., Gray, N. K., & Hentze, M. W. (1995) · PubMed · Cited by 70
Self-citationKugler, W., Enssle, J., Hentze, M. W., & Kulozik, A. E. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.3.413 · Cited by 69
Self-citationEffects of Nonsense Mutations on Nuclear and Cytoplasmic Adenine Phosphoribosyltransferase RNA
Kessler, O., & Chasin, L. A. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.8.4426 · Cited by 65
Determination of mRNA fate by different RNA polymerase II promoters.
Enssle, J., Kugler, W., Hentze, M. W., & Kulozik, A. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.21.10091 · Cited by 64
Self-citationMashima, Y., Murakami, A., Weleber, R. G., Kennaway, N. G., Clarke, L. A., Shiono, T., & Inana, G. (1992) · PubMed · Cited by 63
Cheng, J., Fogel‐Petrovic, M., & Maquat, L. E. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.10.5215-5225.1990 · Cited by 55
Belgrader, P., & Maquat, L. E. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.9.6326-6336.1994 · Cited by 50
Beta‐thalassaemia in the immigrant and non‐immigrant German populations
Vetter, B., Schwarz, C., KOHNE, E., & Kulozik, A. E. (1997) · British Journal of Haematology · doi:10.1046/j.1365-2141.1997.342674.x · Cited by 48
Self-citationT Cell Receptor-β mRNA Splicing: Regulation of Unusual Splicing Intermediates
Qian, L., Theodor, L., Carter, M., Vu, M. N., Sasaki, A. W., & Wilkinson, M. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.3.1686-1696.1993 · Cited by 45
Mammalian Nonsense Codons Can Be cis Effectors of Nuclear mRNA Half-Life
Belgrader, P., Cheng, J., Zhou, X., Stephenson, L. S., & Maquat, L. E. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8219-8228.1994 · Cited by 45
Simpson, S. B., & Stoltzfus, C. M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1835-1844.1994 · Cited by 36
Nonsense mutations and altered splice-site selection.
Dietz, H. C. (1997) · PubMed · Cited by 35
Menon, K. P., & Neufeld, E. F. (1994) · PubMed · Cited by 35
Liu, X., & Mei, J. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.9.1765 · Cited by 25
Site-Directed Mutagenesis Using a Uracil-Containing Phagemid Template
Hagemeier, C. (2003) · Humana Press eBooks · doi:10.1385/0-89603-332-5:45 · Cited by 7
Self-citation
Research works printed but not linked: 2
- Ausubel FM, Brent R, Kingston RI, Moore DD, Seidman JG, Smith JA and Struhl K (1994) Current Protocols in Molecular Biology. Vol. 1. John Wiley, New York.
- Konat GW, Laszkiewicz I, Grubinska B and Wiggins RC (1994) Generation of labelled DNA probes by PCR. In Griffin,H.G. and Griffin,A.M. (eds), PCR Technology. Current Innovations. CRC Press, London, pp. 37–42.
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Dreyfuss, G., Kim, V. N., & Kataoka, N. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm760 · Cited by 1,457
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Azzalin, C. M., Reichenbach, P., Khoriauli, L., Giulotto, E., & Lingner, J. (2007) · Science · doi:10.1126/science.1147182 · Cited by 1,379
The Nonsense-Mediated Decay RNA Surveillance Pathway
Chang, Y.-F., Imam, J. S., & Wilkinson, M. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.050106.093909 · Cited by 1,326
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Maquat, L. E. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1310 · Cited by 1,214
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Frischmeyer, P. A. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.10.1893 · Cited by 991
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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