Journal
CELL
Volume 158, Issue 2, Pages 368-382Publisher
CELL PRESS
DOI: 10.1016/j.cell.2014.05.042
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Funding
- NIH
- Charles A. King Trust
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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 beta 2B-tubulin, known to be required in human neuron and axon migration. We show beta 2B-tubulin is synthesized in axons and localizes preferentially to dynamic microtubules in the growth cone periphery. APC binds the beta 2B-tubulin 3' UTR; experiments interfering with this interaction reduced beta 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.
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