title: 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.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Institute on Aging Intramural Research Program, US National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Hyeon Ho
authors.initials: HH
authors.lastname: Kim
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kuwano
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
authors.forename: Subramanya
authors.initials: S
authors.lastname: Srikantan
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Subaran
authors.forename: Marc
authors.initials: M
authors.lastname: Gleichmann
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Mughal
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.forename: Paul F
authors.initials: PF
authors.lastname: Worley
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
mesh_terms: D020413:3' Untranslated Regions; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002460:Cell Line; D022083:Cytoplasmic Structures / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D016564:Amyloid beta-Protein Precursor; D051860:Fragile X Messenger Ribonucleoprotein 1; D049452:Green Fluorescent Proteins; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse; C485184:enhanced green fluorescent protein
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