Numerous RNAs exhibit specific distribution patterns in mammalian cells. However, the functional and mechanistic consequences are relatively unknown. Here, we investigate the functional role of RNA localization at cellular protrusions of migrating mesenchymal cells, using as a model the RAB13 RNA, which encodes a GTPase important for vesicle‐mediated membrane trafficking. While RAB13 RNA is enriched at peripheral protrusions, the expressed protein is concentrated perinuclearly. By specifically preventing RAB13 RNA localization, we show that peripheral RAB13 translation is not important for the overall distribution of the RAB13 protein or its ability to associate with membranes, but is required for full activation of the GTPase and for efficient cell migration. RAB13 translation leads to a co‐translational association of nascent RAB13 with the exchange factor RABIF. Our results indicate that RAB13‐RABIF association at the periphery is required for directing RAB13 GTPase activity to promote cell migration. Thus, translation of RAB13 in specific subcellular environments imparts the protein with distinct properties and highlights a means of controlling protein function through local RNA translation.

中文翻译：

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RNA 定位和共翻译相互作用控制 RAB13 GTPase 功能和细胞迁移。

许多 RNA 在哺乳动物细胞中表现出特定的分布模式。然而，功能和机械后果相对未知。在这里，我们使用 RAB13 RNA 作为模型，研究 RNA 定位在迁移的间充质细胞的细胞突起中的功能作用，RAB13 RNA 编码对囊泡介导的膜运输很重要的 GTP 酶。虽然 RAB13 RNA 在外周突起处富集，但表达的蛋白质集中在核周。通过特异性阻止 RAB13 RNA 定位，我们表明外周 RAB13 翻译对于 RAB13 蛋白的整体分布或其与膜结合的能力并不重要，但对于 GTPase 的完全激活和有效的细胞迁移是必需的。RAB13 翻译导致新生 RAB13 与交换因子 RABIF 的共翻译关联。我们的结果表明，外围的 RAB13-RABIF 结合是指导 RAB13 GTPase 活性以促进细胞迁移所必需的。因此，RAB13 在特定亚细胞环境中的翻译赋予蛋白质不同的特性，并突出了通过局部 RNA 翻译控制蛋白质功能的方法。