Subcellular localization of messenger RNA (mRNA) is a widespread phenomenon that can impact the regulation and function of the encoded protein. In nonneuronal cells, specific mRNAs localize to cell protrusions, and proper mRNA localization is required for cell migration. However, the mechanisms by which mRNA localization regulates protein function in this setting remain unclear. Here, we examined the functional consequences of localization of the mRNA encoding KIF1C. KIF1C is a kinesin motor protein required for cell migration and mRNA trafficking, including trafficking of its own mRNA. We show that Kif1c mRNA localization does not regulate KIF1C's protein abundance, distribution, or ability to traffic other mRNAs. Conversely, Kif1c mRNA localization to protrusions is required for directed cell migration. We used mass spectrometry to identify binding partners of endogenous KIF1C, which revealed dramatic dysregulation of the number and identity of KIF1C interactors in response to Kif1c mRNA mislocalization. These results therefore uncovered a mechanistic connection between mRNA localization to cell protrusions and the specificity of protein–protein interactions. We anticipate that this mechanism is not limited to Kif1c and is likely to be a general principle that impacts the functions of proteins encoded by protrusion-enriched mRNAs in nonneuronal cells.

中文翻译：

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Kif1c mRNA 定位到细胞突起决定了编码蛋白的结合伙伴特异性

信使 RNA (mRNA) 的亚细胞定位是一种普遍存在的现象，可以影响编码蛋白的调节和功能。在非神经元细胞中，特定的 mRNA 定位于细胞突起，并且细胞迁移需要正确的 mRNA 定位。然而，在这种情况下 mRNA 定位调节蛋白质功能的机制仍不清楚。在这里，我们检查了编码 KIF1C 的 mRNA 定位的功能后果。KIF1C 是细胞迁移和 mRNA 运输所需的驱动蛋白马达蛋白，包括其自身 mRNA 的运输。我们表明Kif1c mRNA 定位不调节 KIF1C 的蛋白质丰度、分布或运输其他 mRNA 的能力。相反，Kif1c定向细胞迁移需要 mRNA 定位到突起。我们使用质谱法来鉴定内源性 KIF1C 的结合伙伴，这揭示了 KIF1C 相互作用因子的数量和身份显着失调以响应Kif1c mRNA 错误定位。因此，这些结果揭示了 mRNA 定位到细胞突起与蛋白质-蛋白质相互作用的特异性之间的机制联系。我们预计这种机制不仅限于Kif1c，而且可能是影响非神经元细胞中富含突起的 mRNA 编码的蛋白质功能的一般原则。