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Ribosome profiling reveals ribosome stalling on tryptophan codons and ribosome queuing upon oxidative stress in fission yeast.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Rubio, Angela 
Ghosh, Sanjay 
Mülleder, Michael 
Ralser, Markus 

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.

Description

Keywords

Cadmium Compounds, Codon, Eukaryotic Initiation Factor-2, Fungal Proteins, Hot Temperature, Hydrogen Peroxide, MAP Kinase Signaling System, Methyl Methanesulfonate, Mitogen-Activated Protein Kinases, Osmotic Pressure, Oxidative Stress, Peptide Chain Elongation, Translational, RNA, Fungal, RNA, Messenger, RNA, Transfer, Trp, Ribosomes, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sorbitol, Sulfates, Tryptophan

Journal Title

Nucleic Acids Res

Conference Name

Journal ISSN

0305-1048
1362-4962

Volume Title

49

Publisher

Oxford University Press (OUP)

Rights

All rights reserved
Sponsorship
BBSRC (BB/N07697/1)
This work was supported by a Biotechnology and Biological Sciences (BBSRC) grant to Juan Mata [BB/N007697/1]. Markus Ralser was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK [FC001134], the UK Medical Research Council [FC001134], and the Wellcome Trust [FC001134], as well as specific project funding from the Wellcome Trust [IA 18 200829/Z/16/Z to M.R.], as well as the German Federal Ministry of Education and Research (BMBF) as part of the National Research Node Mass Spectrometry in Systems Medicine [MSCoreSys 031L0220A].
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