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蛋白质负荷和核输出过载的遗传分析。

Genetic profiling of protein burden and nuclear export overload.

机构信息

Donnelly Center for Cellular and Biomolecular Research, Department of Medical Genetics, University of Toronto, Toronto, Canada.

Research Core for Interdisciplinary Sciences, Okayama University, Okayama, Japan.

出版信息

Elife. 2020 Nov 4;9:e54080. doi: 10.7554/eLife.54080.

DOI:10.7554/eLife.54080
PMID:33146608
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7673788/
Abstract

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.

摘要

蛋白质的过度生产会引发细胞缺陷。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的过载产生的。然而，在蛋白质负担下细胞的生理学特性还没有很好地描述。我们通过系统分析 GFP-op 之间的遗传相互作用，对蛋白质负担进行了遗传分析，同时检测了芽殖酵母中的缺失和温度敏感突变体。我们还在过度生产三倍 GFP（tGFP）和含有核输出信号的 tGFP（NES-tGFP）的细胞中进行了遗传分析。与 GFP-op 特异性相互作用的突变体表明，与肌动蛋白相关的过程（如极化）和蛋白质负担之间存在意想不到的联系，形态分析支持了这一观点。tGFP-op 的相互作用表明，这种蛋白质探针会使蛋白酶体过载，而与 NES-tGFP 相互作用的则涉及编码核输出过程组成部分的基因，为进一步分析蛋白质负担和核输出过载提供了资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef58/7673788/a19916cc8a1a/elife-54080-fig4-figsupp2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef58/7673788/a19916cc8a1a/elife-54080-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef58/7673788/5784b509855e/elife-54080-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef58/7673788/dd24a0e37018/elife-54080-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef58/7673788/bda29f273ce5/elife-54080-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef58/7673788/033b770b00d1/elife-54080-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef58/7673788/cd98f8ad68aa/elife-54080-fig2-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef58/7673788/aadbfea54526/elife-54080-fig2-figsupp5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef58/7673788/4a5df174698e/elife-54080-fig3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef58/7673788/6ec231b7b8c0/elife-54080-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef58/7673788/a19916cc8a1a/elife-54080-fig4-figsupp2.jpg

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