hnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies
Copyright policy )hnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies
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.
- Johns Hopkins Medicine United States
- Johns Hopkins University United States
- National Institute of Health Pakistan
- Johns Hopkins University School of Medicine United States
- National Institutes of Health United States
Mice, Knockout, Neurons, Base Sequence, Heterogeneous-Nuclear Ribonucleoprotein Group C, Green Fluorescent Proteins, Molecular Sequence Data, In Vitro Techniques, Binding, Competitive, Models, Biological, Cell Line, Amyloid beta-Protein Precursor, Fragile X Mental Retardation Protein, Mice, Alzheimer Disease, Genes, Reporter, Protein Biosynthesis, Animals, Cytoplasmic Structures, Humans, 3' Untranslated Regions
Mice, Knockout, Neurons, Base Sequence, Heterogeneous-Nuclear Ribonucleoprotein Group C, Green Fluorescent Proteins, Molecular Sequence Data, In Vitro Techniques, Binding, Competitive, Models, Biological, Cell Line, Amyloid beta-Protein Precursor, Fragile X Mental Retardation Protein, Mice, Alzheimer Disease, Genes, Reporter, Protein Biosynthesis, Animals, Cytoplasmic Structures, Humans, 3' Untranslated Regions
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