RNA binding proteins play critical roles in tumor progression by participating in the post-transcriptional regulation of RNA. However, the levels and function of RBPs in nasopharyngeal carcinoma (NPC) remain elusive. Here we identified a non-canonical RNA binding protein RAN that has the most significant role in NPC progression by a small siRNA pool screening. Functionally, RAN facilitates NPC proliferation and metastasis in vitro and in vivo. High levels of RAN are associated with poor prognosis of NPC patients and can be performed as a prognostic biomarker. Mechanistically, RAN increases the nucleus import of TDP43 and enhances TDP43 nuclear distribution. On the other hand, RAN is directly bound to the coding sequence of G3BP1 mRNA and serves as an adapter to facilitate TDP43 interacting with G3BP1 mRNA 3' untranslated region. These contribute to increasing G3BP1 mRNA stability in the nucleus and lead to up-regulation of G3BP1, which further enhances AKT and ERK signaling and ultimately promotes NPC proliferation and metastasis. These findings reveal that RAN stabilizes intranuclear G3BP1 mRNA by dual mechanisms: recruiting TDP43 into the nucleus and enhancing its interaction with G3BP1 mRNA, suggesting a critical role of RAN in NPC progression and providing a new regulation framework of RBP-RNA.

中文翻译：

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非经典 RNA 结合蛋白 RAN 稳定鼻咽癌核内应激颗粒组装因子 G3BP1 的 mRNA。


RNA 结合蛋白通过参与 RNA 的转录后调控，在肿瘤进展中发挥关键作用。然而，鼻咽癌 （NPC） 中 RBP 的水平和功能仍然难以捉摸。在这里，我们通过小 siRNA 池筛选确定了一种非经典 RNA 结合蛋白 RAN，它在 NPC 进展中起着最重要的作用。在功能上，RAN 在体外和体内促进 NPC 的增殖和转移。高水平的 RAN 与 NPC 患者的不良预后相关，可以作为预后生物标志物进行。从机制上讲，RAN 增加了 TDP43 的细胞核输入并增强了 TDP43 的核分布。另一方面，RAN 直接与 G3BP1 mRNA 的编码序列结合，并作为接头促进 TDP43 与 G3BP1 mRNA 3' 非翻译区相互作用。这些有助于增加细胞核中 G3BP1 mRNA 的稳定性，并导致 G3BP1 的上调，从而进一步增强 AKT 和 ERK 信号传导，并最终促进 NPC 增殖和转移。这些发现揭示了 RAN 通过双重机制稳定核内 G3BP1 mRNA：将 TDP43 募集到细胞核中并增强其与 G3BP1 mRNA 的相互作用，表明 RAN 在 NPC 进展中起关键作用，并为 RBP-RNA 提供了新的调节框架。