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

Author:

Rubio Angela1,Ghosh Sanjay1,Mülleder Michael2,Ralser Markus23,Mata Juan1ORCID

Affiliation:

1. Department of Biochemistry, University of Cambridge, UK

2. The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London, UK

3. Department of Biochemistry, Charité University Medicine, Berlin, Germany

Abstract

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.

Funder

Biotechnology and Biological Sciences

Cancer Research UK

UK Medical Research Council

Wellcome Trust

German Federal Ministry of Education and Research

Publisher

Oxford University Press (OUP)

Subject

Genetics

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