The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress
Summary: Oxidative stress causes K63-linked ubiquitination of ribosomes by the E2 ubiquitin conjugase Rad6. How Rad6-mediated ubiquitination of ribosomes affects translation, however, is unclear. We therefore perform Ribo-seq and Disome-seq in Saccharomyces cerevisiae and show that oxidative stress...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723013712 |
| _version_ | 1797448051458048000 |
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| author | Sezen Meydan Géssica C. Barros Vanessa Simões Lana Harley Blanche K. Cizubu Nicholas R. Guydosh Gustavo M. Silva |
| author_facet | Sezen Meydan Géssica C. Barros Vanessa Simões Lana Harley Blanche K. Cizubu Nicholas R. Guydosh Gustavo M. Silva |
| author_sort | Sezen Meydan |
| collection | DOAJ |
| description | Summary: Oxidative stress causes K63-linked ubiquitination of ribosomes by the E2 ubiquitin conjugase Rad6. How Rad6-mediated ubiquitination of ribosomes affects translation, however, is unclear. We therefore perform Ribo-seq and Disome-seq in Saccharomyces cerevisiae and show that oxidative stress causes ribosome pausing at specific amino acid motifs, which also leads to ribosome collisions. However, these redox-pausing signatures are lost in the absence of Rad6 and do not depend on the ribosome-associated quality control (RQC) pathway. We also show that Rad6 is needed to inhibit overall translation in response to oxidative stress and that its deletion leads to increased expression of antioxidant genes. Finally, we observe that the lack of Rad6 leads to changes during translation that affect activation of the integrated stress response (ISR) pathway. Our results provide a high-resolution picture of the gene expression changes during oxidative stress and unravel an additional stress response pathway affecting translation elongation. |
| first_indexed | 2024-03-09T14:04:47Z |
| format | Article |
| id | doaj.art-60c50936146e4876a458eb95a3f76dfc |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-09T14:04:47Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-60c50936146e4876a458eb95a3f76dfc2023-11-30T05:06:55ZengElsevierCell Reports2211-12472023-11-014211113359The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stressSezen Meydan0Géssica C. Barros1Vanessa Simões2Lana Harley3Blanche K. Cizubu4Nicholas R. Guydosh5Gustavo M. Silva6National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Postdoctoral Research Associate Training Fellowship, National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD 20982, USADepartment of Biology, Duke University, Durham, NC 27708, USADepartment of Biology, Duke University, Durham, NC 27708, USADepartment of Biology, Duke University, Durham, NC 27708, USADepartment of Biology, Duke University, Durham, NC 27708, USANational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding authorDepartment of Biology, Duke University, Durham, NC 27708, USA; Corresponding authorSummary: Oxidative stress causes K63-linked ubiquitination of ribosomes by the E2 ubiquitin conjugase Rad6. How Rad6-mediated ubiquitination of ribosomes affects translation, however, is unclear. We therefore perform Ribo-seq and Disome-seq in Saccharomyces cerevisiae and show that oxidative stress causes ribosome pausing at specific amino acid motifs, which also leads to ribosome collisions. However, these redox-pausing signatures are lost in the absence of Rad6 and do not depend on the ribosome-associated quality control (RQC) pathway. We also show that Rad6 is needed to inhibit overall translation in response to oxidative stress and that its deletion leads to increased expression of antioxidant genes. Finally, we observe that the lack of Rad6 leads to changes during translation that affect activation of the integrated stress response (ISR) pathway. Our results provide a high-resolution picture of the gene expression changes during oxidative stress and unravel an additional stress response pathway affecting translation elongation.http://www.sciencedirect.com/science/article/pii/S2211124723013712CP: Molecular biology |
| spellingShingle | Sezen Meydan Géssica C. Barros Vanessa Simões Lana Harley Blanche K. Cizubu Nicholas R. Guydosh Gustavo M. Silva The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress Cell Reports CP: Molecular biology |
| title | The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress |
| title_full | The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress |
| title_fullStr | The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress |
| title_full_unstemmed | The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress |
| title_short | The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress |
| title_sort | ubiquitin conjugase rad6 mediates ribosome pausing during oxidative stress |
| topic | CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723013712 |
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