New insights into the cellular temporal response to proteostatic stress.
New insights into the cellular temporal response to proteostatic stress.
复制标题
DOI：
10.7554/elife.39054
复制
发表时间：
2018-10-12
期刊：
影响因子：
7.7
通讯作者：
Vogel C
中科院分区：
文献类型：
--
作者：
Rendleman J;Cheng Z;Maity S;Kastelic N;Munschauer M;Allgoewer K;Teo G;Zhang YBM;Lei A;Parker B;Landthaler M;Freeberg L;Kuersten S;Choi H;Vogel C
维持健康的蛋白质组涉及基因表达调控的各个层面。通过量化宫颈癌细胞中转录组、翻译组、蛋白质组和 RNA-蛋白质相互作用组的时间变化，我们系统地表征了应对蛋白质抑制挑战的分子景观。我们确定了对错误折叠蛋白质和氧化应激的共同和特定反应，这两个条件密切相关。我们揭示了未折叠蛋白质反应的新方面，包括许多逃脱全局翻译关闭的基因。这些基因的一个子集支持线粒体能量产生的重新路由。我们还发现许多基因在多个水平、相同或相反的方向以及不同的时间点发生变化。我们重点介绍了多种假定的调控途径，包括氨酰基-tRNA 合成酶的应激依赖性选择性剪接，以及分子伴侣 3' 非翻译区内的蛋白质-RNA 结合。这些结果说明了这种信息丰富的资源的潜力。
Maintaining a healthy proteome involves all layers of gene expression regulation. By quantifying temporal changes of the transcriptome, translatome, proteome, and RNA-protein interactome in cervical cancer cells, we systematically characterize the molecular landscape in response to proteostatic challenges. We identify shared and specific responses to misfolded proteins and to oxidative stress, two conditions that are tightly linked. We reveal new aspects of the unfolded protein response, including many genes that escape global translation shutdown. A subset of these genes supports rerouting of energy production in the mitochondria. We also find that many genes change at multiple levels, in either the same or opposing directions, and at different time points. We highlight a variety of putative regulatory pathways, including the stress-dependent alternative splicing of aminoacyl-tRNA synthetases, and protein-RNA binding within the 3’ untranslated region of molecular chaperones. These results illustrate the potential of this information-rich resource.