title: Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway.
abstract: Fragile X syndrome is caused by a loss of expression of the fragile X mental retardation protein (FMRP). FMRP is a selective RNA-binding protein which forms a messenger ribonucleoprotein (mRNP) complex that associates with polyribosomes. Recently, mRNA ligands associated with FMRP have been identified. However, the mechanism by which FMRP regulates the translation of its mRNA ligands remains unclear. MicroRNAs are small noncoding RNAs involved in translational control. Here we show that in vivo mammalian FMRP interacts with microRNAs and the components of the microRNA pathways including Dicer and the mammalian ortholog of Argonaute 1 (AGO1). Using two different Drosophila melanogaster models, we show that AGO1 is critical for FMRP function in neural development and synaptogenesis. Our results suggest that FMRP may regulate neuronal translation via microRNAs and links microRNAs with human disease.
authors.affiliation: Department of Human Genetics, Emory University, 615 Michael Street, Atlanta, Georgia 30322, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Zarnescu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ceman
authors.forename: Mika
authors.initials: M
authors.lastname: Nakamoto
authors.forename: Julie
authors.initials: J
authors.lastname: Mowrey
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Jongens
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
authors.forename: Kevin
authors.initials: K
authors.lastname: Moses
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Warren
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D015153:Blotting, Western; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D005123:Eye / Q000648:ultrastructure; D005600:Fragile X Syndrome / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000235:genetics; D011233:Precipitin Tests; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism
chemical_list: C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D034743:RNA-Induced Silencing Complex; D043244:Ribonuclease III