HnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies

Eun Kyung Lee, Hyeon Ho Kim, Yuki Kuwano, Kotb Abdelmohsen, Subramanya Srikantan, Sarah S. Subaran, Marc Gleichmann, Mohamed R. Mughal, Jennifer L. Martindale, Xiaoling Yang, Paul F Worley, Mark P. Mattson, Myriam Gorospe

Research output: Contribution to journalArticle

Abstract

Amyloid precursor protein (APP) regulates neuronal synapse function, and its cleavage product AΒ is linked to Alzheimer's disease. Here, we present evidence that the RNA-binding proteins (RBPs) heterogeneous nuclear ribonucleoprotein (hnRNP) C and fragile X mental retardation protein (FMRP) associate with the same APP mRNA coding region element, and they influence APP translation competitively and in opposite directions. Silencing hnRNP C increased FMRP binding to APP mRNA and repressed APP translation, whereas silencing FMRP enhanced hnRNP C binding and promoted translation. Repression of APP translation was linked to colocalization of FMRP and tagged APP RNA within processing bodies; this colocalization was abrogated by hnRNP C overexpression or FMRP silencing. Our findings indicate that FMRP represses translation by recruiting APP mRNA to processing bodies, whereas hnRNP C promotes APP translation by displacing FMRP, thereby relieving the translational block.

Original languageEnglish (US)
Pages (from-to)732-739
Number of pages8
JournalNature structural & molecular biology
Volume17
Issue number6
DOIs
StatePublished - Jun 2010

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ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Lee, E. K., Kim, H. H., Kuwano, Y., Abdelmohsen, K., Srikantan, S., Subaran, S. S., Gleichmann, M., Mughal, M. R., Martindale, J. L., Yang, X., Worley, P. F., Mattson, M. P., & Gorospe, M. (2010). HnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies. Nature structural & molecular biology, 17(6), 732-739. https://doi.org/10.1038/nsmb.1815