학술논문
hnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies.
Document Type
Article
Author
Source
Subject
*AMYLOID beta-protein precursor
*SYNAPSES
*ALZHEIMER'S disease
*MESSENGER RNA
*NUCLEOPROTEINS
*NEUROPLASTICITY
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Language
ISSN
1545-9993
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. [ABSTRACT FROM AUTHOR]