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Distinct types of translation termination generate substrates for ribosome-associated quality control

Cotranslational degradation of polypeptide nascent chains plays a critical role in quality control of protein synthesis and the rescue of stalled ribosomes. In eukaryotes, ribosome stalling triggers release of 60S subunits with attached nascent polypeptides, which undergo ubiquitination by the E3 li...

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Autores principales: Shcherbik, Natalia, Chernova, Tatiana A., Chernoff, Yury O., Pestov, Dimitri G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001609/
https://www.ncbi.nlm.nih.gov/pubmed/27325745
http://dx.doi.org/10.1093/nar/gkw566
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author Shcherbik, Natalia
Chernova, Tatiana A.
Chernoff, Yury O.
Pestov, Dimitri G.
author_facet Shcherbik, Natalia
Chernova, Tatiana A.
Chernoff, Yury O.
Pestov, Dimitri G.
author_sort Shcherbik, Natalia
collection PubMed
description Cotranslational degradation of polypeptide nascent chains plays a critical role in quality control of protein synthesis and the rescue of stalled ribosomes. In eukaryotes, ribosome stalling triggers release of 60S subunits with attached nascent polypeptides, which undergo ubiquitination by the E3 ligase Ltn1 and proteasomal degradation facilitated by the ATPase Cdc48. However, the identity of factors acting upstream in this process is less clear. Here, we examined how the canonical release factors Sup45–Sup35 (eRF1–eRF3) and their paralogs Dom34-Hbs1 affect the total population of ubiquitinated nascent chains associated with yeast ribosomes. We found that the availability of the functional release factor complex Sup45–Sup35 strongly influences the amount of ubiquitinated polypeptides associated with 60S ribosomal subunits, while Dom34-Hbs1 generate 60S-associated peptidyl-tRNAs that constitute a relatively minor fraction of Ltn1 substrates. These results uncover two separate pathways that target nascent polypeptides for Ltn1-Cdc48-mediated degradation and suggest that in addition to canonical termination on stop codons, eukaryotic release factors contribute to cotranslational protein quality control.
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spelling pubmed-50016092016-12-07 Distinct types of translation termination generate substrates for ribosome-associated quality control Shcherbik, Natalia Chernova, Tatiana A. Chernoff, Yury O. Pestov, Dimitri G. Nucleic Acids Res Molecular Biology Cotranslational degradation of polypeptide nascent chains plays a critical role in quality control of protein synthesis and the rescue of stalled ribosomes. In eukaryotes, ribosome stalling triggers release of 60S subunits with attached nascent polypeptides, which undergo ubiquitination by the E3 ligase Ltn1 and proteasomal degradation facilitated by the ATPase Cdc48. However, the identity of factors acting upstream in this process is less clear. Here, we examined how the canonical release factors Sup45–Sup35 (eRF1–eRF3) and their paralogs Dom34-Hbs1 affect the total population of ubiquitinated nascent chains associated with yeast ribosomes. We found that the availability of the functional release factor complex Sup45–Sup35 strongly influences the amount of ubiquitinated polypeptides associated with 60S ribosomal subunits, while Dom34-Hbs1 generate 60S-associated peptidyl-tRNAs that constitute a relatively minor fraction of Ltn1 substrates. These results uncover two separate pathways that target nascent polypeptides for Ltn1-Cdc48-mediated degradation and suggest that in addition to canonical termination on stop codons, eukaryotic release factors contribute to cotranslational protein quality control. Oxford University Press 2016-08-19 2016-06-20 /pmc/articles/PMC5001609/ /pubmed/27325745 http://dx.doi.org/10.1093/nar/gkw566 Text en © The Author(s) 2016. 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 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
Shcherbik, Natalia
Chernova, Tatiana A.
Chernoff, Yury O.
Pestov, Dimitri G.
Distinct types of translation termination generate substrates for ribosome-associated quality control
title Distinct types of translation termination generate substrates for ribosome-associated quality control
title_full Distinct types of translation termination generate substrates for ribosome-associated quality control
title_fullStr Distinct types of translation termination generate substrates for ribosome-associated quality control
title_full_unstemmed Distinct types of translation termination generate substrates for ribosome-associated quality control
title_short Distinct types of translation termination generate substrates for ribosome-associated quality control
title_sort distinct types of translation termination generate substrates for ribosome-associated quality control
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001609/
https://www.ncbi.nlm.nih.gov/pubmed/27325745
http://dx.doi.org/10.1093/nar/gkw566
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