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Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding
BACKGROUND: The folding of proteins is challenging in the highly crowded and sticky environment of a cell. Regulation of translation elongation may play a crucial role in ensuring the correct folding of proteins. Much of our knowledge regarding translation elongation comes from the sequencing of mRN...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784341/ https://www.ncbi.nlm.nih.gov/pubmed/33402206 http://dx.doi.org/10.1186/s13059-020-02256-0 |
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author | Zhao, Taolan Chen, Yan-Ming Li, Yu Wang, Jia Chen, Siyu Gao, Ning Qian, Wenfeng |
author_facet | Zhao, Taolan Chen, Yan-Ming Li, Yu Wang, Jia Chen, Siyu Gao, Ning Qian, Wenfeng |
author_sort | Zhao, Taolan |
collection | PubMed |
description | BACKGROUND: The folding of proteins is challenging in the highly crowded and sticky environment of a cell. Regulation of translation elongation may play a crucial role in ensuring the correct folding of proteins. Much of our knowledge regarding translation elongation comes from the sequencing of mRNA fragments protected by single ribosomes by ribo-seq. However, larger protected mRNA fragments have been observed, suggesting the existence of an alternative and previously hidden layer of regulation. RESULTS: In this study, we performed disome-seq to sequence mRNA fragments protected by two stacked ribosomes, a product of translational pauses during which the 5′-elongating ribosome collides with the 3′-paused one. We detected widespread ribosome collisions that are related to slow ribosome release when stop codons are at the A-site, slow peptide bond formation from proline, glycine, asparagine, and cysteine when they are at the P-site, and slow leaving of polylysine from the exit tunnel of ribosomes. The structure of disomes obtained by cryo-electron microscopy suggests a different conformation from the substrate of the ribosome-associated protein quality control pathway. Collisions occurred more frequently in the gap regions between α-helices, where a translational pause can prevent the folding interference from the downstream peptides. Paused or collided ribosomes are associated with specific chaperones, which can aid in the cotranslational folding of the nascent peptides. CONCLUSIONS: Therefore, cells use regulated ribosome collisions to ensure protein homeostasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-020-02256-0. |
format | Online Article Text |
id | pubmed-7784341 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-77843412021-01-14 Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding Zhao, Taolan Chen, Yan-Ming Li, Yu Wang, Jia Chen, Siyu Gao, Ning Qian, Wenfeng Genome Biol Research BACKGROUND: The folding of proteins is challenging in the highly crowded and sticky environment of a cell. Regulation of translation elongation may play a crucial role in ensuring the correct folding of proteins. Much of our knowledge regarding translation elongation comes from the sequencing of mRNA fragments protected by single ribosomes by ribo-seq. However, larger protected mRNA fragments have been observed, suggesting the existence of an alternative and previously hidden layer of regulation. RESULTS: In this study, we performed disome-seq to sequence mRNA fragments protected by two stacked ribosomes, a product of translational pauses during which the 5′-elongating ribosome collides with the 3′-paused one. We detected widespread ribosome collisions that are related to slow ribosome release when stop codons are at the A-site, slow peptide bond formation from proline, glycine, asparagine, and cysteine when they are at the P-site, and slow leaving of polylysine from the exit tunnel of ribosomes. The structure of disomes obtained by cryo-electron microscopy suggests a different conformation from the substrate of the ribosome-associated protein quality control pathway. Collisions occurred more frequently in the gap regions between α-helices, where a translational pause can prevent the folding interference from the downstream peptides. Paused or collided ribosomes are associated with specific chaperones, which can aid in the cotranslational folding of the nascent peptides. CONCLUSIONS: Therefore, cells use regulated ribosome collisions to ensure protein homeostasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-020-02256-0. BioMed Central 2021-01-05 /pmc/articles/PMC7784341/ /pubmed/33402206 http://dx.doi.org/10.1186/s13059-020-02256-0 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Zhao, Taolan Chen, Yan-Ming Li, Yu Wang, Jia Chen, Siyu Gao, Ning Qian, Wenfeng Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding |
title | Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding |
title_full | Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding |
title_fullStr | Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding |
title_full_unstemmed | Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding |
title_short | Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding |
title_sort | disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784341/ https://www.ncbi.nlm.nih.gov/pubmed/33402206 http://dx.doi.org/10.1186/s13059-020-02256-0 |
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