PHAX (Phosphorylated adaptor for RNA export) promotes nuclear export of short transcripts of RNA polymerase II such as spliceosomal U snRNA precursors, as well as intra-nuclear transport of small nucleolar RNAs (snoRNAs). However, it remains unknown whether PHAX has other critical functions. Here we show that PHAX is required for efficient DNA damage response (DDR) via regulation of phosphorylated histone variant H2AX (γH2AX), a key factor for DDR. Knockdown of PHAX led to a significant reduction of H2AX mRNA levels, through inhibition of both transcription of H2AX gene and nuclear export of H2AX mRNA, one of the shortest mRNAs in the cell. As a result, PHAX-knockdown cells become more sensitive to DNA damage due to a shortage of γH2AX. These results reveal a novel function of PHAX, which secures efficient DDR and hence genome stability.

中文翻译：

---

RNA 转运因子 PHAX 是正确的组蛋白 H2AX 表达和 DNA 损伤反应所必需的

PHAX（用于 RNA 输出的磷酸化接头）促进 RNA 聚合酶 II 的短转录物的核输出，例如剪接体 U snRNA 前体，以及小核仁 RNA (snoRNA) 的核内转运。然而，PHAX 是否还有其他关键功能仍然未知。在这里，我们表明 PHAX 是通过调节磷酸化组蛋白变体 H2AX（γH2AX）（DDR 的一个关键因素）来实现有效 DNA 损伤反应 (DDR) 所必需的。通过抑制 H2AX 基因的转录和 H2AX mRNA（细胞中最短的 mRNA 之一）的核输出，敲除 PHAX 导致 H2AX mRNA 水平显着降低。因此，由于缺乏 γH2AX，PHAX 敲低细胞对 DNA 损伤变得更加敏感。这些结果揭示了 PHAX 的新功能，它确保了有效的 DDR，从而确保了基因组的稳定性。