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


ABSTRACT: Amyloid precursor protein (APP) regulates neuronal synapse function, and its cleavage product Abeta 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.

SUBMITTER: Lee EK 

PROVIDER: S-EPMC2908492 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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

Lee Eun Kyung EK   Kim Hyeon Ho HH   Kuwano Yuki Y   Abdelmohsen Kotb K   Srikantan Subramanya S   Subaran Sarah S SS   Gleichmann Marc M   Mughal Mohamed R MR   Martindale Jennifer L JL   Yang Xiaoling X   Worley Paul F PF   Mattson Mark P MP   Gorospe Myriam M  

Nature structural & molecular biology 20100516 6


Amyloid precursor protein (APP) regulates neuronal synapse function, and its cleavage product Abeta 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 t  ...[more]

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