Ribosome quality control is a central protection mechanism for yeast exposed to deoxynivalenol and trichothecin.
Ribosome quality control is a central protection mechanism for yeast exposed to deoxynivalenol and trichothecin.
复制标题
核糖体质量控制是暴露于脱氧烯醇和毛刺素的酵母中心保护机制。
DOI：
10.1186/s12864-016-2718-y
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发表时间：
2016-06-01
期刊：
影响因子：
4.4
通讯作者：
Schüller C
中科院分区：
文献类型：
--
作者：
Kugler KG;Jandric Z;Beyer R;Klopf E;Glaser W;Lemmens M;Shams M;Mayer K;Adam G;Schüller C
脱氧雪腐镰刀菌烯醇（DON）和喜树碱（TTC）是真核生物蛋白质合成的抑制剂。它们对细胞内稳态的影响知之甚少。我们报告了一个系统的功能调查的影响DON和TTC的酵母酿酒酵母基因芯片，网络和微阵列分析。为了将遗传分析集中在毒素作用的细胞内后果上，我们排除了编码强效多效性药物外排蛋白的PDR 5基因，这可能混淆结果。因此，我们使用了具有pdr 5 Δ菌株背景的敲除文库。DON或TTC处理产生了与核糖体效率相关的适应性瓶颈。通过系统遗传阵列分析分离的基因在核糖体质量控制、翻译保真度和转录中有助于毒素抗性功能。E3连接酶Hel 2的突变体，参与核糖体质量控制，和Rpd 3组蛋白脱乙酰酶复合物的几个成员对DON高度敏感。DON和TTC具有相似的遗传特征，尽管它们的毒性不同。网络分析表明，DON和TTC抗性赋予基因产物之间的遗传相互作用的连贯和紧密的网络。这些网络表现出通常与有效处理信息相关的拓扑特性。许多敏感突变体具有“缓慢生长”基因表达特征。暴露于DON的酵母细胞增加核糖体蛋白和组蛋白基因的转录，指示生长增强的内部信号。基因表达谱和突变体分析的组合揭示了在DON和TTC胁迫下成为瓶颈的细胞途径。这些通常与核糖体生物合成直接或间接相关，如一般分泌途径、细胞骨架、细胞周期延迟、核糖体合成和翻译质量控制。基因表达谱表明核糖体成分的需求增加，并没有揭示应激途径的激活。我们的分析突出了核糖体质量控制和组蛋白脱乙酰酶复合物的贡献作为对DON和TTC的抗性的主要来源。本文的在线版本（doi：10.1186/s12864-016-2718-y）包含补充材料，可供授权用户使用。
The trichothecene mycotoxins deoxynivalenol (DON) and trichothecin (TTC) are inhibitors of eukaryotic protein synthesis. Their effect on cellular homeostasis is poorly understood. We report a systematic functional investigation of the effect of DON and TTC on the yeast Saccharomyces cerevisiae using genetic array, network and microarray analysis. To focus the genetic analysis on intracellular consequences of toxin action we eliminated the PDR5 gene coding for a potent pleiotropic drug efflux protein potentially confounding results. We therefore used a knockout library with a pdr5Δ strain background. DON or TTC treatment creates a fitness bottleneck connected to ribosome efficiency. Genes isolated by systematic genetic array analysis as contributing to toxin resistance function in ribosome quality control, translation fidelity, and in transcription. Mutants in the E3 ligase Hel2, involved in ribosome quality control, and several members of the Rpd3 histone deacetylase complex were highly sensitive to DON. DON and TTC have similar genetic profiles despite their different toxic potency. Network analysis shows a coherent and tight network of genetic interactions among the DON and TTC resistance conferring gene products. The networks exhibited topological properties commonly associated with efficient processing of information. Many sensitive mutants have a "slow growth" gene expression signature. DON-exposed yeast cells increase transcripts of ribosomal protein and histone genes indicating an internal signal for growth enhancement. The combination of gene expression profiling and analysis of mutants reveals cellular pathways which become bottlenecks under DON and TTC stress. These are generally directly or indirectly connected to ribosome biosynthesis such as the general secretory pathway, cytoskeleton, cell cycle delay, ribosome synthesis and translation quality control. Gene expression profiling points to an increased demand of ribosomal components and does not reveal activation of stress pathways. Our analysis highlights ribosome quality control and a contribution of a histone deacetylase complex as main sources of resistance against DON and TTC. The online version of this article (doi:10.1186/s12864-016-2718-y) contains supplementary material, which is available to authorized users.
影响因子：
5.6
作者：
Iwahashi, Yumiko;Kitagawa, Emiko;Iwahashi, Hitoshi
通讯作者：
Iwahashi, Hitoshi