The integrated stress response is a network of highly orchestrated pathways activated when cells are exposed to environmental stressors. While global repression of translation is a well-recognized hallmark of the integrated stress response, less is known about the regulation of mRNA stability during stress. DEAD box proteins are a family of RNA unwinding/remodeling enzymes involved in every aspect of RNA metabolism. We previously showed that DEAD box 1 (DDX1) protein accumulates at DNA double-strand breaks during genotoxic stress and promotes DNA double-strand break repair via homologous recombination. Here, we examine the role of DDX1 in response to environmental stress. We show that DDX1 is recruited to stress granules (SGs) in cells exposed to a variety of environmental stressors, including arsenite, hydrogen peroxide, and thapsigargin. We also show that DDX1 depletion delays resolution of arsenite-induced SGs. Using RNA immunoprecipitation sequencing, we identify RNA targets bound to endogenous DDX1, including RNAs transcribed from genes previously implicated in stress responses. We show the amount of target RNAs bound to DDX1 increases when cells are exposed to stress, and the overall levels of these RNAs are increased during stress in a DDX1-dependent manner. Even though DDX1’s RNA-binding property is critical for maintenance of its target mRNA levels, we found RNA binding is not required for localization of DDX1 to SGs. Furthermore, DDX1 knockdown does not appear to affect RNA localization to SGs. Taken together, our results reveal a novel role for DDX1 in maintaining cytoplasmic mRNA levels in cells exposed to oxidative stress.

综合应激反应是一个高度协调的通路网络，当细胞暴露于环境压力源时会被激活。虽然翻译的全局抑制是综合应激反应的公认标志，但对应激期间 mRNA 稳定性的调节知之甚少。死盒蛋白是涉及 RNA 代谢各个方面的 RNA 解旋/重塑酶家族。我们之前表明，DEAD box 1 (DDX1) 蛋白在基因毒性应激期间在 DNA 双链断裂处积累，并通过促进 DNA 双链断裂修复同源重组。在这里，我们研究了 DDX1 在应对环境压力中的作用。我们表明 DDX1 被招募到暴露于各种环境压力源（包括亚砷酸盐、过氧化氢和毒胡萝卜素）的细胞中的应激颗粒 (SG)。我们还表明 DDX1 耗尽延迟了亚砷酸盐诱导的 SGs 的分辨率。使用 RNA 免疫沉淀测序，我们确定了与内源性 DDX1 结合的 RNA 靶标，包括从先前与应激反应有关的基因转录的 RNA。我们显示当细胞暴露于压力时，与 DDX1 结合的靶 RNA 的数量会增加，并且这些 RNA 的总体水平在压力期间以 DDX1 依赖性方式增加。尽管 DDX1 的 RNA 结合特性对于维持其目标 mRNA 水平至关重要，我们发现将 DDX1 定位到 SG 不需要 RNA 结合。此外，DDX1 敲低似乎不会影响 SG 的 RNA 定位。总之，我们的结果揭示了 DDX1 在维持暴露于氧化应激的细胞中的细胞质 mRNA 水平方面的新作用。