APC Is an RNA-binding Protein, and Its Interactome Provides a Link to Neural Development and Microtubule Assembly

Cell. 2014 Jul 17;158(2):368-382. doi: 10.1016/j.cell.2014.05.042.

Abstract

Adenomatous polyposis coli (APC) is a microtubule plus-end scaffolding protein important in biology and disease. APC is implicated in RNA localization, although the mechanisms and functional significance remain unclear. We show APC is an RNA-binding protein and identify an RNA interactome by HITS-CLIP. Targets were highly enriched for APC-related functions, including microtubule organization, cell motility, cancer, and neurologic disease. Among the targets is β2B-tubulin, known to be required in human neuron and axon migration. We show β2B-tubulin is synthesized in axons and localizes preferentially to dynamic microtubules in the growth cone periphery. APC binds the β2B-tubulin 3' UTR; experiments interfering with this interaction reduced β2B-tubulin mRNA axonal localization and expression, depleted dynamic microtubules and the growth cone periphery, and impaired neuron migration. These results identify APC as a platform binding functionally related protein and RNA networks, and suggest a self-organizing model for the microtubule to localize synthesis of its own subunits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / metabolism*
  • Animals
  • Axons / metabolism
  • Base Sequence
  • Brain / cytology
  • Brain / metabolism
  • Cell Line
  • Cell Movement
  • Ganglia, Spinal / cytology
  • Genome-Wide Association Study
  • Growth Cones / metabolism
  • Mice
  • Microtubules / metabolism*
  • Molecular Sequence Data
  • Neurogenesis*
  • Neurons / metabolism
  • Protein Interaction Maps
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Rats
  • Sequence Alignment
  • Tubulin / metabolism

Substances

  • Adenomatous Polyposis Coli Protein
  • RNA, Messenger
  • RNA-Binding Proteins
  • Tubulin

Associated data

  • SRA/SRP042131