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Translational read-through promotes aggregation and shapes stop codon identity
Faithful translation of genetic information depends on the ability of the translational machinery to decode stop codons as termination signals. Although termination of protein synthesis is highly efficient, errors in decoding of stop codons may lead to the synthesis of C-terminally extended proteins...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144920/ https://www.ncbi.nlm.nih.gov/pubmed/32128584 http://dx.doi.org/10.1093/nar/gkaa136 |
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author | Kramarski, Lior Arbely, Eyal |
author_facet | Kramarski, Lior Arbely, Eyal |
author_sort | Kramarski, Lior |
collection | PubMed |
description | Faithful translation of genetic information depends on the ability of the translational machinery to decode stop codons as termination signals. Although termination of protein synthesis is highly efficient, errors in decoding of stop codons may lead to the synthesis of C-terminally extended proteins. It was found that in eukaryotes such elongated proteins do not accumulate in cells. However, the mechanism for sequestration of C-terminally extended proteins is still unknown. Here we show that 3′-UTR-encoded polypeptides promote aggregation of the C-terminally extended proteins, and targeting to lysosomes. We demonstrate that 3′-UTR-encoded polypeptides can promote different levels of protein aggregation, similar to random sequences. We also show that aggregation of endogenous proteins can be induced by aminoglycoside antibiotics that promote stop codon read-through, by UAG suppressor tRNA, or by knokcdown of release factor 1. Furthermore, we find correlation between the fidelity of termination signals, and the predicted propensity of downstream 3′-UTR-encoded polypeptides to form intrinsically disordered regions. Our data highlight a new quality control mechanism for elimination of C-terminally elongated proteins. |
format | Online Article Text |
id | pubmed-7144920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-71449202020-04-13 Translational read-through promotes aggregation and shapes stop codon identity Kramarski, Lior Arbely, Eyal Nucleic Acids Res Molecular Biology Faithful translation of genetic information depends on the ability of the translational machinery to decode stop codons as termination signals. Although termination of protein synthesis is highly efficient, errors in decoding of stop codons may lead to the synthesis of C-terminally extended proteins. It was found that in eukaryotes such elongated proteins do not accumulate in cells. However, the mechanism for sequestration of C-terminally extended proteins is still unknown. Here we show that 3′-UTR-encoded polypeptides promote aggregation of the C-terminally extended proteins, and targeting to lysosomes. We demonstrate that 3′-UTR-encoded polypeptides can promote different levels of protein aggregation, similar to random sequences. We also show that aggregation of endogenous proteins can be induced by aminoglycoside antibiotics that promote stop codon read-through, by UAG suppressor tRNA, or by knokcdown of release factor 1. Furthermore, we find correlation between the fidelity of termination signals, and the predicted propensity of downstream 3′-UTR-encoded polypeptides to form intrinsically disordered regions. Our data highlight a new quality control mechanism for elimination of C-terminally elongated proteins. Oxford University Press 2020-04-17 2020-03-04 /pmc/articles/PMC7144920/ /pubmed/32128584 http://dx.doi.org/10.1093/nar/gkaa136 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Molecular Biology Kramarski, Lior Arbely, Eyal Translational read-through promotes aggregation and shapes stop codon identity |
title | Translational read-through promotes aggregation and shapes stop codon identity |
title_full | Translational read-through promotes aggregation and shapes stop codon identity |
title_fullStr | Translational read-through promotes aggregation and shapes stop codon identity |
title_full_unstemmed | Translational read-through promotes aggregation and shapes stop codon identity |
title_short | Translational read-through promotes aggregation and shapes stop codon identity |
title_sort | translational read-through promotes aggregation and shapes stop codon identity |
topic | Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144920/ https://www.ncbi.nlm.nih.gov/pubmed/32128584 http://dx.doi.org/10.1093/nar/gkaa136 |
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