Cells sense, respond, and adapt to environmental conditions that cause stress. In a previous study using HeLa cells, we isolated reporter cells responding to the endoplasmic reticulum (ER) stress inducers, thapsigargin and tunicamycin, using a highly sensitive promoter trap vector system. Splinkerette PCR and 5′ rapid amplification of cDNA ends (5′ RACE) identified a novel transcript that is upregulated by ER stress. Its endogenous expression increased approximately 10-fold in response to thapsigargin and tunicamycin within 1 h, but was down-regulated after 4 h. Because the transcript starts from an intron of a long noncoding RNA known as we designated the newly identified transcript (ranscript nduced by tressors from ocus). was also expressed under several other stress conditions. It was particularly increased > 10-fold upon glucose starvation and 7-fold by arsenite exposure. Furthermore, analyses, including a ChIP-atlas search, revealed that there is an ATF4-binding region with a c/ebp-Atf response element (CARE) downstream of the transcription start site of . Based on these results, we hypothesized that may be induced by the phospho-eIF2α and ATF4- axis of the integrated stress response pathway, which is known to be activated by the stress conditions listed above. As expected, knockout of abolished the stress-induced upregulation of . Our results indicate that may be a useful biomarker for detecting stress conditions that activate ATF4. Our highly sensitive trap vector system proved beneficial in discovering new biomarkers.

中文翻译：

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刺激 ATF4 的应激源上调的新型 RNA 转录本 TISPL 的鉴定

细胞感知、响应并适应引起压力的环境条件。在之前使用 HeLa 细胞的研究中，我们使用高度敏感的启动子捕获载体系统分离了对内质网 (ER) 应激诱导剂毒胡萝卜素和衣霉素作出反应的报告细胞。 Splinkerette PCR 和 cDNA 末端 5' 快速扩增 (5' RACE) 鉴定出一种新的转录物，该转录物会因 ER 应激而上调。在毒胡萝卜素和衣霉素的作用下，其内源表达在 1 小时内增加约 10 倍，但在 4 小时后下调。因为转录本起始于长非编码RNA的内含子，我们将其称为新鉴定的转录本（由来自ocus的tressors诱导的转录本）。在其他几种应激条件下也有表达。尤其是在葡萄糖饥饿时增加了 10 倍以上，在接触亚砷酸盐时增加了 7 倍。此外，包括 ChIP-atlas 搜索在内的分析表明，在 的转录起始位点下游存在一个带有 ac/ebp-Atf 响应元件 (CARE) 的 ATF4 结合区域。基于这些结果，我们假设这可能是由整合应激反应途径的磷酸化 eIF2α 和 ATF4 轴诱导的，已知该途径是由上面列出的应激条件激活的。正如预期的那样，敲除 消除了应激诱导的上调。我们的结果表明，这可能是检测激活 ATF4 的应激条件的有用生物标志物。事实证明，我们的高度灵敏的捕获载体系统有助于发现新的生物标志物。