In cells, mRNAs are transported to and positioned at subcellular areas to locally regulate protein production. Recent studies have identified the kinesin-3 family member motor protein KIF1C as an RNA transporter. However, it is not clear how KIF1C interacts with RNA molecules. Here, we show that the KIF1C C-terminal tail domain contains an intrinsically disordered region (IDR) that drives liquid-liquid phase separation (LLPS). KIF1C forms dynamic puncta in cells that display physical properties of liquid condensates and incorporate RNA molecules in a sequence-selective manner. Endogenous KIF1C forms condensates in cellular protrusions, where mRNAs are enriched in an IDR-dependent manner. Purified KIF1C tail constructs undergo LLPS in vitro at near-endogenous nM concentrations and in the absence of crowding agents and can directly recruit RNA molecules. Overall, our work uncovers an intrinsic correlation between the LLPS activity of KIF1C and its role in mRNA positioning. In addition, the LLPS activity of KIF1C's tail represents a new mode of motor-cargo interaction that extends our current understanding of cytoskeletal motor proteins.

中文翻译：

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kinesin-3 KIF1C 经历液-液相分离，以在细胞外周积累特定转录物。


在细胞中，mRNA 被运输并定位于亚细胞区域，以局部调节蛋白质的产生。最近的研究已确定驱动蛋白 3 家族成员运动蛋白 KIF1C 是一种 RNA 转运蛋白。然而，目前尚不清楚 KIF1C 如何与 RNA 分子相互作用。在这里，我们发现 KIF1C C 末端尾部结构域包含驱动液-液相分离 (LLPS) 的本质无序区域 (IDR)。 KIF1C 在细胞中形成动态斑点，显示出液体凝聚物的物理特性，并以序列选择性方式掺入 RNA 分子。内源性 KIF1C 在细胞突起中形成凝聚物，其中 mRNA 以 IDR 依赖性方式富集。纯化的 KIF1C 尾构建体在体外以接近内源 nM 的浓度且在没有拥挤剂的情况下进行 LLPS，并且可以直接招募 RNA 分子。总的来说，我们的工作揭示了 KIF1C 的 LLPS 活性与其在 mRNA 定位中的作用之间的内在相关性。此外，KIF1C 尾部的 LLPS 活性代表了一种新的运动-货物相互作用模式，扩展了我们目前对细胞骨架运动蛋白的理解。