Programmed Cell Death 4 (PDCD4) protein is a tumour suppressor that inhibits translation through the mTOR dependent initiation factor EIF4A, but its functional role and mRNA targets in neurons remain largely unknown. Our work identified that PDCD4 is highly expressed in axons and dendrites of CNS and PNS neurons, with loss and gain of function experiments in cortical and dorsal root ganglia primary neurons demonstrating the capacity of PDCD4 to negatively control axonal growth. To explore PDCD4 transcriptome and translatome targets we used Ribo-Seq and uncovered a list of potential targets with known functions as axon/neurite outgrowth regulators. In addition, we observed that PDCD4 can be locally synthesized in adult axons in vivo and its levels decrease at the site of peripheral nerve injury and before nerve regeneration. Overall, our findings demonstrate that PDCD4 can act as a new regulator of axonal growth via the selective control of translation, providing a target mechanism for axon regeneration and neuronal plasticity processes in neurons.

中文翻译：

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PDCD4 通过神经突生长相关基因的翻译抑制来调节轴突生长，并在神经损伤反应过程中受到调节

程序性细胞死亡 4 (PDCD4) 蛋白是一种肿瘤抑制因子，可通过 mTOR 依赖性起始因子 EIF4A 抑制翻译，但其在神经元中的功能作用和 mRNA 靶标仍然很大程度上未知。我们的工作确定 PDCD4 在 CNS 和 PNS 神经元的轴突和树突中高度表达，皮质和背根神经节初级神经元的功能丧失和获得实验证明了 PDCD4 负控制轴突生长的能力。为了探索 PDCD4 转录组和翻译组目标，我们使用了 Ribo-Seq 并发现了一系列具有轴突/神经突生长调节因子已知功能的潜在目标。此外，我们观察到 PDCD4 可以在体内成体轴突局部合成，其水平在周围神经损伤部位和神经再生之前降低。全面的，