| Literature DB >> 20473314 |
Eun Kyung Lee1, 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.
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.Entities:
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Year: 2010 PMID： 20473314 PMCID： PMC2908492 DOI： 10.1038/nsmb.1815
Source DB: PubMed Journal: Nat Struct Mol Biol ISSN： 1545-9985 Impact factor: 15.369