PDF(Pubmed)
Abstract：
Some chemotherapy drugs modulate the formation of stress granules (SGs), which are RNA-containing cytoplasmic foci contributing to stress response pathways. How SGs mechanistically contribute to pro-survival or pro-apoptotic functions must be better defined. The chemotherapy drug lomustine promotes SG formation by activating the stress-sensing eIF2α kinase HRI (encoded by the EIF2AK1 gene). Here, we applied a DNA microarray-based transcriptome analysis to determine the genes modulated by lomustine-induced stress and suggest roles for SGs in this process. We found that the expression of the pro-apoptotic EGR1 gene was specifically regulated in cells upon lomustine treatment. The appearance of EGR1-encoding mRNA in SGs correlated with a decrease in EGR1 mRNA translation. Specifically, EGR1 mRNA was sequestered to SGs upon lomustine treatment, probably preventing its ribosome translation and consequently limiting the degree of apoptosis. Our data support the model where SGs can selectively sequester specific mRNAs in a stress-specific manner, modulate their availability for translation, and thus determine the fate of a stressed cell.
摘要：
一些化疗药物调节应激颗粒（SGs）的形成，它们是含有RNA的细胞质灶，有助于应激反应途径。必须更好地定义SGs如何在机械上促进生存或促凋亡功能。化疗药物洛莫司汀通过激活应激感应eIF2α激酶HRI（由EIF2AK1基因编码）促进SG形成。这里,我们应用基于DNA微阵列的转录组分析来确定洛莫司汀诱导的应激调节的基因,并提出SGs在这一过程中的作用.我们发现，洛莫司汀处理后，促凋亡EGR1基因的表达在细胞中受到特异性调节。SGs中编码EGR1的mRNA的出现与EGR1mRNA翻译的减少有关。具体来说,在洛莫司汀治疗后，EGR1mRNA被隔离到SGs中，可能阻止其核糖体翻译，从而限制细胞凋亡的程度。我们的数据支持SGs可以以应激特异性方式选择性地隔离特定mRNA的模型，调节它们的翻译可用性，从而决定了一个应激细胞的命运.
