Genome Biology
Abstract
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.
| 论文编号: | DOI:10.1186/s13059-020-02256-0 |
| 论文题目: | Disome-seq Reveals Widespread Ribosome Collisions that Promote Cotranslational Protein Folding |
| 英文论文题目: | Disome-seq Reveals Widespread Ribosome Collisions that Promote Cotranslational Protein Folding |
| 第一作者: | Taolan Zhao, Yan-Ming Chen, Yu Li, Jia Wang, Siyu Chen, Ning Gao and Wenfeng Qian |
| 英文第一作者: | Taolan Zhao, Yan-Ming Chen, Yu Li, Jia Wang, Siyu Chen, Ning Gao and Wenfeng Qian |
| 联系作者: | |
| 英文联系作者: | |
| 外单位作者单位: | |
| 英文外单位作者单位: | |
| 发表年度: | 2021-01-11 |
| 卷: | |
| 期: | |
| 页码: | |
| 摘要: | 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. |
| 英文摘要: | 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. |
| 刊物名称: | Genome Biology |
| 英文刊物名称: | Genome Biology |
| 论文全文: | |
| 英文论文全文: | |
| 全文链接: | |
| 其它备注: | Taolan Zhao, Yan-Ming Chen, Yu Li, Jia Wang, Siyu Chen, Ning Gao and Wenfeng Qian. Disome-seq Reveals Widespread Ribosome Collisions that Promote Cotranslational Protein Folding. Genome Biology. DOI:10.1186/s13059-020-02256-0 |
| 英文其它备注: | |
| 学科: | |
| 英文学科: | |
| 影响因子: | |
| 第一作者所在部门: | |
| 英文第一作者所在部门: | |
| 论文出处: | |
| 英文论文出处: | |
| 论文类别: | |
| 英文论文类别: | |
| 参与作者: | |
| 英文参与作者: |
