Ribosome profiling reveals ribosome stalling on tryptophan codons and ribosome queuing upon oxidative stress in fission yeast.
Ribosome profiling reveals ribosome stalling on tryptophan codons and ribosome queuing upon oxidative stress in fission yeast.
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DOI：
10.1093/nar/gkaa1180
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发表时间：
2021-01-11
影响因子：
14.9
通讯作者：
Mata J
中科院分区：
文献类型：
--
作者：
Rubio A;Ghosh S;Mülleder M;Ralser M;Mata J
翻译控制在应激反应中是必不可少的。我们研究了裂殖酵母粟酒裂殖酵母在五种环境压力下的翻译程序。我们还探讨了防御途径对这些方案的贡献：调节翻译起始的综合应激反应（ISR）和应激反应MAPK途径。我们进行了核糖体分析的细胞受到每种压力，在野生型细胞和细胞的防御途径失活。转录因子Fil 1是酵母Gcn 4和哺乳动物Atf 4蛋白的功能同源物，其表达上调，并且是对大多数应激反应所必需的。此外，许多编码核糖体生物合成所需蛋白质的mRNA被抑制性下调。因此，几种压力触发普遍的翻译反应，包括减少核糖体的生产和Fil 1介导的转录程序。令人惊讶的是，核糖体在氧化应激时停滞在色氨酸密码子上，这可能是由于带电荷的tRNA-色氨酸减少。停滞引起色氨酸密码子上游的核糖体积累（核糖体排队/碰撞），表明停滞的核糖体影响其他核糖体的翻译延伸。一致的是，色氨酸密码子停滞导致翻译延长减少，并有助于ISR介导的起始抑制。我们发现，不同的压力引起共同的和特定的翻译反应，揭示了一个新的作用色氨酸-tRNA的可用性。
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.
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