Polarised targeting of diverse mRNAs to cellular protrusions is a hallmark of cell migration. Although a widespread phenomenon, definitive functions for endogenous targeted mRNAs and their relevance to modulation of in vivo tissue dynamics remain elusive. Here, using single‐molecule analysis, gene editing and zebrafish live‐cell imaging, we report that mRNA polarisation acts as a molecular compass that orients motile cell polarity and spatially directs tissue movement. Clustering of protrusion‐derived RNAseq datasets defined a core 192‐nt localisation element underpinning precise mRNA targeting to sites of filopodia formation. Such targeting of the small GTPase RAB13 generated tight spatial coupling of mRNA localisation, translation and protein activity, achieving precise subcellular compartmentalisation of RAB13 protein function to create a polarised domain of filopodia extension. Consequently, genomic excision of this localisation element and perturbation of RAB13 mRNA targeting—but not translation—depolarised filopodia dynamics in motile endothelial cells and induced mispatterning of blood vessels in zebrafish. Hence, mRNA polarisation, not expression, is the primary determinant of the site of RAB13 action, preventing ectopic functionality at inappropriate subcellular loci and orienting tissue morphogenesis.

中文翻译：

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RAB13 mRNA 区室化在空间上定向组织形态发生。

不同 mRNA 对细胞突起的极化靶向是细胞迁移的标志。虽然是一种普遍现象，但内源性靶向 mRNA 的明确功能及其与体内调节的相关性 组织动力学仍然难以捉摸。在这里，使用单分子分析、基因编辑和斑马鱼活细胞成像，我们报告了 mRNA 极化作为分子罗盘，可以定位运动细胞极性并在空间上指导组织运动。突起衍生的 RNAseq 数据集的聚类定义了一个核心的 192-nt 定位元素，支持将 mRNA 精确定位到丝状伪足形成部位。这种对小 GTPase RAB13 的靶向产生了 mRNA 定位、翻译和蛋白质活性的紧密空间耦合，实现了 RAB13 蛋白质功能的精确亚细胞区室化，从而产生了丝状伪足延伸的极化结构域。因此，这种定位元件的基因组切除和RAB13的扰动 mRNA 靶向 - 但不是翻译 - 去极化运动内皮细胞中的丝状伪足动力学并诱导斑马鱼血管的错误模式。因此，mRNA 极化而非表达是 RAB13 作用位点的主要决定因素，防止在不适当的亚细胞位点发生异位功能并定向组织形态发生。