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The ribosome quality control pathway can access nascent polypeptides stalled at the Sec61 translocon
Cytosolic ribosomes that stall during translation are split into subunits, and nascent polypeptides trapped in the 60S subunit are ubiquitinated by the ribosome quality control (RQC) pathway. Whether the RQC pathway can also target stalls during cotranslational translocation into the ER is not known...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462936/ https://www.ncbi.nlm.nih.gov/pubmed/25877867 http://dx.doi.org/10.1091/mbc.E15-01-0040 |
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author | von der Malsburg, Karina Shao, Sichen Hegde, Ramanujan S. |
author_facet | von der Malsburg, Karina Shao, Sichen Hegde, Ramanujan S. |
author_sort | von der Malsburg, Karina |
collection | PubMed |
description | Cytosolic ribosomes that stall during translation are split into subunits, and nascent polypeptides trapped in the 60S subunit are ubiquitinated by the ribosome quality control (RQC) pathway. Whether the RQC pathway can also target stalls during cotranslational translocation into the ER is not known. Here we report that listerin and NEMF, core RQC components, are bound to translocon-engaged 60S subunits on native ER membranes. RQC recruitment to the ER in cultured cells is stimulated by translation stalling. Biochemical analyses demonstrated that translocon-targeted nascent polypeptides that subsequently stall are polyubiquitinated in 60S complexes. Ubiquitination at the translocon requires cytosolic exposure of the polypeptide at the ribosome–Sec61 junction. This exposure can result from either failed insertion into the Sec61 channel or partial backsliding of translocating nascent chains. Only Sec61-engaged nascent chains early in their biogenesis were relatively refractory to ubiquitination. Modeling based on recent 60S–RQC and 80S–Sec61 structures suggests that the E3 ligase listerin accesses nascent polypeptides via a gap in the ribosome–translocon junction near the Sec61 lateral gate. Thus the RQC pathway can target stalled translocation intermediates for degradation from the Sec61 channel. |
format | Online Article Text |
id | pubmed-4462936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-44629362015-08-30 The ribosome quality control pathway can access nascent polypeptides stalled at the Sec61 translocon von der Malsburg, Karina Shao, Sichen Hegde, Ramanujan S. Mol Biol Cell Articles Cytosolic ribosomes that stall during translation are split into subunits, and nascent polypeptides trapped in the 60S subunit are ubiquitinated by the ribosome quality control (RQC) pathway. Whether the RQC pathway can also target stalls during cotranslational translocation into the ER is not known. Here we report that listerin and NEMF, core RQC components, are bound to translocon-engaged 60S subunits on native ER membranes. RQC recruitment to the ER in cultured cells is stimulated by translation stalling. Biochemical analyses demonstrated that translocon-targeted nascent polypeptides that subsequently stall are polyubiquitinated in 60S complexes. Ubiquitination at the translocon requires cytosolic exposure of the polypeptide at the ribosome–Sec61 junction. This exposure can result from either failed insertion into the Sec61 channel or partial backsliding of translocating nascent chains. Only Sec61-engaged nascent chains early in their biogenesis were relatively refractory to ubiquitination. Modeling based on recent 60S–RQC and 80S–Sec61 structures suggests that the E3 ligase listerin accesses nascent polypeptides via a gap in the ribosome–translocon junction near the Sec61 lateral gate. Thus the RQC pathway can target stalled translocation intermediates for degradation from the Sec61 channel. The American Society for Cell Biology 2015-06-15 /pmc/articles/PMC4462936/ /pubmed/25877867 http://dx.doi.org/10.1091/mbc.E15-01-0040 Text en © 2015 von der Malsburg et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles von der Malsburg, Karina Shao, Sichen Hegde, Ramanujan S. The ribosome quality control pathway can access nascent polypeptides stalled at the Sec61 translocon |
title | The ribosome quality control pathway can access nascent polypeptides stalled at the Sec61 translocon |
title_full | The ribosome quality control pathway can access nascent polypeptides stalled at the Sec61 translocon |
title_fullStr | The ribosome quality control pathway can access nascent polypeptides stalled at the Sec61 translocon |
title_full_unstemmed | The ribosome quality control pathway can access nascent polypeptides stalled at the Sec61 translocon |
title_short | The ribosome quality control pathway can access nascent polypeptides stalled at the Sec61 translocon |
title_sort | ribosome quality control pathway can access nascent polypeptides stalled at the sec61 translocon |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462936/ https://www.ncbi.nlm.nih.gov/pubmed/25877867 http://dx.doi.org/10.1091/mbc.E15-01-0040 |
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