Ribosome profiling reveals ribosome stalling on tryptophan codons and ribosome queuing upon oxidative stress in fission yeast
- PMID: 33313903
- PMCID: PMC7797079
- DOI: 10.1093/nar/gkaa1180
Ribosome profiling reveals ribosome stalling on tryptophan codons and ribosome queuing upon oxidative stress in fission yeast
Abstract
Translational control is essential in response to stress. We investigated the translational programmes launched by the fission yeast Schizosaccharomyces pombe upon five environmental stresses. We also explored the contribution of defence pathways to these programmes: The Integrated Stress Response (ISR), which regulates translation initiation, and the stress-response MAPK pathway. We performed ribosome profiling of cells subjected to each stress, in wild type cells and in cells with the defence pathways inactivated. The transcription factor Fil1, a functional homologue of the yeast Gcn4 and the mammalian Atf4 proteins, was translationally upregulated and required for the response to most stresses. Moreover, many mRNAs encoding proteins required for ribosome biogenesis were translationally downregulated. Thus, several stresses trigger a universal translational response, including reduced ribosome production and a Fil1-mediated transcriptional programme. Surprisingly, ribosomes stalled on tryptophan codons upon oxidative stress, likely due to a decrease in charged tRNA-Tryptophan. Stalling caused ribosome accumulation upstream of tryptophan codons (ribosome queuing/collisions), demonstrating that stalled ribosomes affect translation elongation by other ribosomes. Consistently, tryptophan codon stalling led to reduced translation elongation and contributed to the ISR-mediated inhibition of initiation. We show that different stresses elicit common and specific translational responses, revealing a novel role in Tryptophan-tRNA availability.
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
Figures
Similar articles
-
Fission yeast mitogen-activated protein kinase Sty1 interacts with translation factors.Eukaryot Cell. 2008 Feb;7(2):328-38. doi: 10.1128/EC.00358-07. Epub 2007 Dec 7. Eukaryot Cell. 2008. PMID: 18065650 Free PMC article.
-
Role of mitogen-activated protein kinase Sty1 in regulation of eukaryotic initiation factor 2alpha kinases in response to environmental stress in Schizosaccharomyces pombe.Eukaryot Cell. 2010 Jan;9(1):194-207. doi: 10.1128/EC.00185-09. Epub 2009 Oct 30. Eukaryot Cell. 2010. PMID: 19880757 Free PMC article.
-
Polyamine Control of Translation Elongation Regulates Start Site Selection on Antizyme Inhibitor mRNA via Ribosome Queuing.Mol Cell. 2018 Apr 19;70(2):254-264.e6. doi: 10.1016/j.molcel.2018.03.015. Mol Cell. 2018. PMID: 29677493 Free PMC article.
-
The ribosome in action: Tuning of translational efficiency and protein folding.Protein Sci. 2016 Aug;25(8):1390-406. doi: 10.1002/pro.2950. Epub 2016 Jun 8. Protein Sci. 2016. PMID: 27198711 Free PMC article. Review.
-
Regulation of translation initiation by amino acids in eukaryotic cells.Prog Mol Subcell Biol. 2001;26:155-84. doi: 10.1007/978-3-642-56688-2_6. Prog Mol Subcell Biol. 2001. PMID: 11575165 Review.
Cited by
-
Stalled translation by mitochondrial stress upregulates a CNOT4-ZNF598 ribosomal quality control pathway important for tissue homeostasis.Nat Commun. 2024 Feb 22;15(1):1637. doi: 10.1038/s41467-024-45525-3. Nat Commun. 2024. PMID: 38388640 Free PMC article.
-
Ribosome profiling: a powerful tool in oncological research.Biomark Res. 2024 Jan 25;12(1):11. doi: 10.1186/s40364-024-00562-4. Biomark Res. 2024. PMID: 38273337 Free PMC article. Review.
-
The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress.Cell Rep. 2023 Nov 28;42(11):113359. doi: 10.1016/j.celrep.2023.113359. Epub 2023 Nov 2. Cell Rep. 2023. PMID: 37917585 Free PMC article.
-
Is there a localized role for translational quality control?RNA. 2023 Nov;29(11):1623-1643. doi: 10.1261/rna.079683.123. Epub 2023 Aug 15. RNA. 2023. PMID: 37582617 Free PMC article.
-
Contributions of Ccr4 and Gcn2 to the Translational Response of C. neoformans to Host-Relevant Stressors and Integrated Stress Response Induction.mBio. 2023 Apr 25;14(2):e0019623. doi: 10.1128/mbio.00196-23. Epub 2023 Apr 5. mBio. 2023. PMID: 37017529 Free PMC article.
References
-
- Spriggs K.A., Bushell M., Willis A.E.. Translational regulation of gene expression during conditions of cell stress. Mol. Cell. 2010; 40:228–237. - PubMed
-
- Tahmasebi S., Khoutorsky A., Mathews M.B., Sonenberg N.. Translation deregulation in human disease. Nat. Rev. Mol. Cell Biol. 2018; 19:791–807. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
