Arginine and glutamate rich 1 (ARGLU1) is a poorly understood cellular protein with functions in RNA splicing and transcription. Computational prediction suggests that ARGLU1 contains intrinsically disordered regions and lacks any known structural or functional domains. We used adenovirus Early protein 1A (E1A) to probe for critical regulators of important cellular pathways and identified ARGLU1 as a significant player in transcription and the DNA damage response pathway. Transcriptional effects induced by ARGLU1 occur via enhancement of promoter-proximal RNA polymerase II pausing, likely by inhibiting the interaction between JMJD6 and BRD4. When overexpressed, ARGLU1 increases the growth rate of cancer cells, while its knockdown leads to growth arrest. Significantly, overexpression of ARGLU1 increased cancer cell resistance to genotoxic drugs and promoted DNA damage repair. These results identify new roles for ARGLU1 in cancer cell survival and the DNA damage repair pathway, with potential clinical implications for chemotherapy resistance.

中文翻译：

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ARGLU1 增强 RNA 聚合酶 II 启动子近端暂停并刺激 DNA 损伤修复

富含精氨酸和谷氨酸 1 (ARGLU1) 是一种人们知之甚少的细胞蛋白，其在 RNA 剪接和转录中发挥着作用。计算预测表明 ARGLU1 包含本质上无序的区域，并且缺乏任何已知的结构或功能域。我们使用腺病毒早期蛋白 1A (E1A) 来探测重要细胞通路的关键调节因子，并确定 ARGLU1 在转录和 DNA 损伤反应通路中发挥着重要作用。 ARGLU1 诱导的转录效应是通过增强启动子近端 RNA 聚合酶 II 暂停而发生的，可能是通过抑制 JMJD6 和 BRD4 之间的相互作用来实现的。当过度表达时，ARGLU1 会增加癌细胞的生长速度，而其敲低则会导致生长停滞。值得注意的是，ARGLU1 的过度表达增加了癌细胞对基因毒性药物的抵抗力并促进 DNA 损伤修复。这些结果确定了 ARGLU1 在癌细胞存活和 DNA 损伤修复途径中的新作用，对化疗耐药具有潜在的临床意义。