WD repeat domain 77 protein (WDR77) is required for cellular proliferation of lung and prostate epithelial cells during earlier stages of development and is reactivated during prostate and lung tumorigenesis. WDR77 plays an essential role in prostate tumorigenesis and cell growth mediated by growth regulatory factors. Here, we identified E2F1 and E2F3 mRNAs as translational targets of WDR77. We demonstrated that WDR77 regulated the translation of E2F1 and E2F3 mRNAs through the 5′ untranslated regions (UTRs) of E2F1 and E2F3 (E2F1/3) mRNAs. WDR77 physically interacted with programmed cell death 4 (PDCD4) that suppresses translation of mRNAs containing structured 5′ UTRs by interacting with eukaryotic translation initiation factor 4A (eIF4A) and inhibiting its helicase activity. Further, we demonstrated that the interaction between WDR77 and PDCD4 prevented the binding of PDCD4 to eIF4A and relieved PDCD4's inhibitory effect on eIF4A1. Overall, our work reveals for the first time that WDR77 is directly involved in translational regulation of E2F1/3 mRNAs through their structured 5′ UTRs, PDCD4, and eIF4A1 and provides novel insight into the cell growth controlled by WDR77.

中文翻译：

---

WD重复域77蛋白调节E2F1和E2F3 mRNA的翻译

WD重复域77蛋白（WDR77）在发育的早期阶段是肺和前列腺上皮细胞的细胞增殖所必需的，并且在前列腺和肺肿瘤发生过程中被重新激活。WDR77在前列腺癌的发生和由生长调节因子介导的细胞生长中起着至关重要的作用。在这里，我们确定E2F1和E2F3 mRNA作为WDR77的翻译目标。我们证明了WDR77通过E2F1和E2F3（E2F1 / 3）mRNA的5'非翻译区（UTR）调节E2F1和E2F3 mRNA的翻译。WDR77与程序性细胞死亡4（PDCD4）发生物理相互作用，该程序通过与真核翻译起始因子4A（eIF4A）相互作用并抑制其解旋酶活性来抑制包含结构化5'UTR的mRNA的翻译。进一步，我们证明了WDR77与PDCD4之间的相互作用阻止了PDCD4与eIF4A的结合并减轻了PDCD4对eIF4A1的抑制作用。总的来说，我们的工作首次揭示了WDR77通过其结构化的5'UTR，PDCD4和eIF4A1直接参与E2F1 / 3 mRNA的翻译调控，并为WDR77控制的细胞生长提供了新颖的见解。