Genetic profiling of protein burden and nuclear export overload.
Genetic profiling of protein burden and nuclear export overload.
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DOI：
10.7554/elife.54080
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发表时间：
2020-11-04
期刊：
影响因子：
7.7
通讯作者：
Moriya H
中科院分区：
文献类型：
--
作者：
Kintaka R;Makanae K;Namba S;Kato H;Kito K;Ohnuki S;Ohya Y;Andrews BJ;Boone C;Moriya H
蛋白质的过度生产(OP)会引发细胞缺陷。过度生产的后果之一是蛋白质负担/成本，这是由蛋白质合成过程超负荷产生的。然而，细胞在蛋白质负荷下的生理学特征并不是很好。我们通过系统分析GFP-OP之间的遗传相互作用来进行蛋白质负荷的遗传图谱分析，调查了芽期酵母中的缺失和温度敏感突变。我们还对过量产生三重GFP(TGFP)和含有核输出信号的tGFP(NES-tGFP)的细胞进行了遗传图谱分析。与GFP-OP特异相互作用的突变体暗示了肌动蛋白相关过程之间意想不到的联系，如极化和蛋白质负荷，这一点得到了形态分析的支持。TGFP-OP的相互作用表明，该蛋白质探针使蛋白酶体超载，而与NES-tGFP相互作用的探针涉及编码核输出过程组件的基因，为进一步分析蛋白质负荷和核输出超载提供了资源。
Overproduction (op) of proteins triggers cellular defects. One of the consequences of overproduction is the protein burden/cost, which is produced by an overloading of the protein synthesis process. However, the physiology of cells under a protein burden is not well characterized. We performed genetic profiling of protein burden by systematic analysis of genetic interactions between GFP-op, surveying both deletion and temperature-sensitive mutants in budding yeast. We also performed genetic profiling in cells with overproduction of triple-GFP (tGFP), and the nuclear export signal-containing tGFP (NES-tGFP). The mutants specifically interacted with GFP-op were suggestive of unexpected connections between actin-related processes like polarization and the protein burden, which was supported by morphological analysis. The tGFP-op interactions suggested that this protein probe overloads the proteasome, whereas those that interacted with NES-tGFP involved genes encoding components of the nuclear export process, providing a resource for further analysis of the protein burden and nuclear export overload.