The kinesin KIF1C transports APC-dependent mRNAs to cell protrusions

RNA. 2021 Dec;27(12):1528-1544. doi: 10.1261/rna.078576.120. Epub 2021 Sep 7.

Abstract

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.

Keywords: RNA localization; RNA transport; cytoplasmic protrusions; local translation.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism*
  • Animals
  • Cell Surface Extensions / metabolism*
  • Cytoplasm / metabolism*
  • HeLa Cells
  • Humans
  • Kinesins / genetics
  • Kinesins / metabolism*
  • RNA Transport*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*

Substances

  • Adenomatous Polyposis Coli Protein
  • KIF1C protein, human
  • Kif1c protein, mouse
  • RNA, Messenger
  • Kinesins