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APC is an RNA-binding protein, and its interactome provides a link to neural development and microtubule assembly.
Preitner, Nicolas; Quan, Jie; Nowakowski, Dan W; Hancock, Melissa L; Shi, Jianhua; Tcherkezian, Joseph; Young-Pearse, Tracy L; Flanagan, John G.
Afiliación
  • Preitner N; Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
  • Quan J; Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
  • Nowakowski DW; Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
  • Hancock ML; Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
  • Shi J; Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
  • Tcherkezian J; Laboratory for Therapeutic Development, Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Young-Pearse TL; Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Flanagan JG; Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA. Electronic address: flanagan@hms.harvard.edu.
Cell ; 158(2): 368-382, 2014 Jul 17.
Article en En | MEDLINE | ID: mdl-25036633
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 ß2B-tubulin, known to be required in human neuron and axon migration. We show ß2B-tubulin is synthesized in axons and localizes preferentially to dynamic microtubules in the growth cone periphery. APC binds the ß2B-tubulin 3' UTR; experiments interfering with this interaction reduced ß2B-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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas de Unión al ARN / Proteína de la Poliposis Adenomatosa del Colon / Neurogénesis / Microtúbulos Límite: Animals Idioma: En Revista: Cell Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas de Unión al ARN / Proteína de la Poliposis Adenomatosa del Colon / Neurogénesis / Microtúbulos Límite: Animals Idioma: En Revista: Cell Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos