The kinesin KIF1C transports APC-dependent mRNAs to cell protrusions.

The kinesin KIF1C transports APC-dependent mRNAs to cell protrusions.
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DOI:
10.1261/rna.078576.120
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发表时间:
2021-12
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
Mili S
Mili S
中科院分区:
其他
文献类型:
--
作者:
Pichon X;Moissoglu K;Coleno E;Wang T;Imbert A;Robert MC;Peter M;Chouaib R;Walter T;Mueller F;Zibara K;Bertrand E;Mili S

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RNA定位和局部翻译对许多细胞功能都很重要。在哺乳动物中,一类mRNA以依赖腺瘤性结肠息肉病蛋白(APC)的方式定位到细胞质突起,在细胞迁移过程中发挥作用。在此,我们研究了这种定位机制。我们发现驱动蛋白KIF1C与依赖APC的mRNA相互作用,并且是它们定位所必需的。活细胞成像显示单个mRNA在长距离上快速、主动运输,这需要微管和KIF1C。双色成像直接显示单个KIF1C驱动蛋白运输单个mRNA,3′非翻译区(3′UTR)足以触发依赖KIF1C的RNA运输和定位。此外,KIF1C与周边的多聚体RNA簇保持关联,并且是它们形成所必需的。这些结果揭示了哺乳动物细胞中一种广泛存在的RNA运输途径,其中KIF1C驱动蛋白在运输RNA以及将它们聚集在细胞质突起内具有双重作用。有趣的是,KIF1C也运输其自身的mRNA,这表明在mRNA运输水平可能存在一个反馈回路。
RNA localization and local translation are important for numerous cellular functions. In mammals, a class of mRNAs localize to cytoplasmic protrusions in an APC-dependent manner, with roles during cell migration. Here, we investigated this localization mechanism. We found that the KIF1C motor interacts with APC-dependent mRNAs and is required for their localization. Live cell imaging revealed rapid, active transport of single mRNAs over long distances that requires both microtubules and KIF1C. Two-color imaging directly revealed single mRNAs transported by single KIF1C motors, with the 3′UTR being sufficient to trigger KIF1C-dependent RNA transport and localization. Moreover, KIF1C remained associated with peripheral, multimeric RNA clusters and was required for their formation. These results reveal a widespread RNA transport pathway in mammalian cells, in which the KIF1C motor has a dual role in transporting RNAs and clustering them within cytoplasmic protrusions. Interestingly, KIF1C also transports its own mRNA, suggesting a possible feedback loop acting at the level of mRNA transport.
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