APC is an RNA-binding protein, and its interactome provides a link to neural development and microtubule assembly.

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 ?2B-tubulin, known to be required in human neuron and axon migration. We show ?2B-tubulin is synthesized in axons and localizes preferentially to dynamic microtubules in the growth cone periphery. APC binds the ?2B-tubulin 3' UTR; experiments interfering with this interaction reduced ?2B-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.

SUBMITTER: Preitner N 

PROVIDER: S-EPMC4133101 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature