Ribosome profiling reveals ribosome stalling on tryptophan codons upon oxidative stress in fission yeast
Ribosome profiling reveals ribosome stalling on tryptophan codons upon oxidative stress in fission yeast
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核糖体分析揭示了裂殖酵母中氧化应激时核糖体在色氨酸密码子上的停滞
DOI：
10.1101/2020.04.23.054833
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Rubio A
中科院分区：
文献类型：
--
作者：
Rubio A
翻译的调节是对应激条件的一种基本反应。我们研究了裂殖酵母在五种环境胁迫下启动的翻译程序：氧化应激、重金属、热休克、渗透休克和DNA损伤。我们还探讨了两条主要的防御途径对这些程序的贡献：直接调节翻译启动的整合应激反应和应激反应MAPK途径。为了获得这一现象的全基因组和高分辨率视图，我们对对照细胞和受到上述五种胁迫的细胞进行了核糖体图谱分析，无论是在野生型背景下还是在整合应激反应或MAPK途径失活的细胞中。翻译变化部分依赖于两条信号通路的完整性。有趣的是，我们发现转录因子Fil1是Gcn4和ATF4蛋白(分别来自萌芽酵母和哺乳动物)的功能同源物，在大多数胁迫下高度上调。与这一结果一致的是，对大多数压力的正常反应都需要Fil1。一大组mRNA在翻译上下调，包括核糖体生物发生所需的许多。总体而言，我们的数据表明，严重的应激导致普遍的翻译反应的实施，其中包括节能措施(减少核糖体的生产)和诱导Fil1介导的转录程序。令人惊讶的是，核糖体停滞在色氨酸密码子上，特别是在氧化应激下，这一现象可能是由带电的tRNA-色氨酸减少引起的。色氨酸停滞导致轻微的翻译伸长减少，并有助于抑制整合应激反应的启动。综上所述，我们的结果表明，不同的压力引起共同和特定的翻译反应，揭示了在色氨酸-tRNA的可获得性中一个特殊的、迄今未知的作用。
Modulation of translation is an essential response to stress conditions. We have investigated the translational programmes launched by the fission yeastSchizosaccharomyces pombesubject to five environmental stresses: oxidative stress, heavy metal, heat shock, osmotic shock and DNA damage. We also explored the contribution of two major defence pathways to these programmes: The Integrated Stress Response, which directly regulates translation initiation, and the stress-response MAPK pathway. To obtain a genome-wide and high-resolution view of this phenomenon, we performed ribosome profiling of control cells and of cells subject to each of the five stresses mentioned above, both in wild type background and in cells in which the Integrated Stress Response or the MAPK pathway were inactivated.Translational changes were partially dependent on the integrity of both signalling pathways. Interestingly, we found that the transcription factor Fil1, a functional homologue of the Gcn4 and Atf4 proteins (from budding yeast and mammals, respectively), was highly upregulated in most stresses. Consistent with this result, Fil1 was required for the normal response to most stresses. A large group of mRNAs were translationally downregulated, including many required for ribosome biogenesis. Overall, our data suggest that severe stresses lead to the implementation of a universal translational response, which includes energy-saving measures (reduction of ribosome production) and induction of a Fil1-mediated transcriptional programme.Surprisingly, ribosomes stalled on tryptophan codons specifically upon oxidative stress, a phenomenon that is likely caused by a decrease in charged tRNA-Tryptophan. Tryptophan stalling led to a mild translation elongation reduction and contributed to the inhibition of initiation by the Integrated Stress Response. Taken together, our results show that different stresses elicit common and specific translational responses, revealing a special and so far unknown role in Tryptophan-tRNA availability.
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DOI：
10.1038/nsb1015
发表时间：
2003-12-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Preiss, T;Baron-Benhamou, J;Hentze, MW
通讯作者：
Hentze, MW
癌症中蛋白质合成、能量代谢和自噬之间的串扰。
影响因子：
4
作者：
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通讯作者：
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影响因子：
10.5
作者：
Pavitt, GD;Ramaiah, KVA;Hinnebusch, AG
通讯作者：
Hinnebusch, AG
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DOI：
--
发表时间：
1999
期刊：
Journal of Biochemistry (Tokyo)
影响因子：
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作者：
R. Ohmiya;Chinatsu Kato;Hisami Yamada;H. Aiba;Takeshi Mizuno
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DOI：
10.1007/978-1-61779-949-5_19
发表时间：
2012
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
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作者：
Janssen, Brian D;Diner, Elie J;Hayes, Christopher S
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Hayes, Christopher S