Various species of non-coding RNAs (ncRNAs) are enriched in specific subcellular compartments, but the mechanisms orchestrating their localization and their local functions remain largely unknown. We investigated both aspects using the elongating retinal ganglion cell axon and its tip, the growth cone, as models. We reveal that specific endogenous precursor microRNAs (pre-miRNAs) are actively trafficked to distal axons by hitchhiking primarily on late endosomes/lysosomes. Upon exposure to the axon guidance cue semaphorin 3A (Sema3A), pre-miRNAs are processed specifically within axons into newly generated miRNAs, one of which, in turn, silences the basal translation of tubulin beta 3 class III (TUBB3), but not amyloid beta precursor protein (APP). At the organismal level, these mature miRNAs are required for growth cone steering and a fully functional visual system. Overall, our results uncover a novel mode of ncRNA transport from one cytosolic compartment to another within polarized cells. They also reveal that newly generated miRNAs are critical components of a ncRNA-based signaling pathway that transduces environmental signals into the structural remodeling of subcellular compartments.

中文翻译：

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轴突前体miRNA在内体上搭便车并局部调节神经回路的发育。

各种非编码RNA（ncRNA）丰富了特定的亚细胞区室，但是协调它们的定位和其局部功能的机制在很大程度上仍然未知。我们使用伸长的视网膜神经节细胞轴突及其尖端（生长锥）作为模型来研究这两个方面。我们揭示特定的内源性前体microRNA（pre-miRNA）主要通过在晚期内体/溶酶体上搭便车而积极地运输到远端轴突。暴露于轴突导向提示信号蛋白3A（Sema3A）后，pre-miRNA在轴突内被专门加工成新生成的miRNA，其中之一反过来沉默了微管蛋白beta 3 III类（TUBB3）的基础翻译，但没有淀粉样蛋白β前体蛋白（APP）。在机体层面，这些成熟的miRNA是生长锥操纵和功能齐全的视觉系统所必需的。总体而言，我们的研究结果揭示了ncRNA从极化细胞内的一个胞浆区室转移到另一个胞质区室的新模式。他们还揭示了新生成的miRNA是基于ncRNA的信号传导途径的关键组成部分，该信号传导途径将环境信号转导至亚细胞区室的结构重塑。