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

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

Author information

1
Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
2
Laboratory for Therapeutic Development, Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 1Y6, Canada.
3
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
4
Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA. Electronic address: flanagan@hms.harvard.edu.

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.

PMID:
25036633
PMCID:
PMC4133101
DOI:
10.1016/j.cell.2014.05.042
[Indexed for MEDLINE]
Free PMC Article

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