title: 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 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.
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Preitner
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Quan
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Dan W
authors.initials: DW
authors.lastname: Nowakowski
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Hancock
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Shi
authors.affiliation: Laboratory for Therapeutic Development, Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 1Y6, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Tcherkezian
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Young-Pearse
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA. Electronic address: flanagan@hms.harvard.edu.
authors.forename: John G
authors.initials: JG
authors.lastname: Flanagan
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D005727:Ganglia, Spinal / Q000166:cytology; D055106:Genome-Wide Association Study; D020439:Growth Cones / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D060066:Protein Interaction Maps; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D016415:Sequence Alignment; D014404:Tubulin / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014404:Tubulin