Axonal precursor miRNAs hitchhike on endosomes and locally regulate the development of neural circuits
Axonal precursor miRNAs hitchhike on endosomes and locally regulate the development of neural circuits
复制标题
DOI：
10.15252/embj.2019102513
复制
发表时间：
2020-02-19
期刊：
影响因子：
11.4
通讯作者：
Baudet, Marie-Laure
中科院分区：
文献类型：
--
作者：
Corradi, Eloina;Dalla Costa, Irene;Baudet, Marie-Laure
不同种类的非编码RNA（ncRNA）在特定的亚细胞区室中富集，但是协调它们的定位和它们的局部功能的机制在很大程度上仍然未知。我们研究了这两个方面使用伸长的视网膜神经节细胞轴突和它的尖端，生长锥，作为模型。我们发现，特定的内源性前体microRNA（前-miRNA）被积极贩运到远端轴突搭便车主要是在晚期内体/溶酶体。当暴露于轴突引导因子脑信号蛋白3A（Sema 3A）时，前体miRNA在轴突内被特异性加工成新生成的miRNA，其中之一反过来沉默微管蛋白β 3 III类（TUBB 3）的基础翻译，但不沉默淀粉样蛋白β前体蛋白（APP）。在生物体水平上，这些成熟的miRNAs是生长锥转向和功能齐全的视觉系统所必需的。总的来说，我们的研究结果揭示了一种新的模式的ncRNA运输从一个胞质隔室到另一个极化细胞内。他们还揭示了新产生的miRNA是基于ncRNA的信号通路的关键组分，该通路将环境信号转导到亚细胞区室的结构重塑中。
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.