Cited by 406RNA Research and SplicingRNA and protein synthesis mechanismsHemoglobinopathies and Related Disorders

Binary specification of nonsense codons by splicing and cytoplasmic translation

Open access
Thermann, Rolf, Neu‐Yilik, Gabriele, Deters, Andrea, Frede, Ute, Wehr, Kristina, Hagemeier, Christian, Hentze, Matthias W., Kulozik, Andreas E.·1998·The EMBO Journal

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/emboj/17.12.3484

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Ausubel,F.M., Brent,R., Kingston,R.I., Moore,D.D., Seidman,J.G., Smith,J.A. and Struhl,K. (1994) Current Protocols in Molecular Biology. Vol. 1. John Wiley, New York.
  2. Konat,G.W., Laszkiewicz,I., Grubinska,B. and Wiggins,R.C. (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.

Cited by

Sorted by citations

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
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
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 › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review