title: Genetic modifiers of dFMR1 encode RNA granule components in Drosophila.
abstract: Mechanisms of neuronal mRNA localization and translation are of considerable biological interest. Spatially regulated mRNA translation contributes to cell-fate decisions and axon guidance during development, as well as to long-term synaptic plasticity in adulthood. The Fragile-X Mental Retardation protein (FMRP/dFMR1) is one of the best-studied neuronal translational control molecules and here we describe the identification and early characterization of proteins likely to function in the dFMR1 pathway. Induction of the dFMR1 in sevenless-expressing cells of the Drosophila eye causes a disorganized (rough) eye through a mechanism that requires residues necessary for dFMR1/FMRP's translational repressor function. Several mutations in dco, orb2, pAbp, rm62, and smD3 genes dominantly suppress the sev-dfmr1 rough-eye phenotype, suggesting that they are required for dFMR1-mediated processes. The encoded proteins localize to dFMR1-containing neuronal mRNPs in neurites of cultured neurons, and/or have an effect on dendritic branching predicted for bona fide neuronal translational repressors. Genetic mosaic analyses indicate that dco, orb2, rm62, smD3, and dfmr1 are dispensable for translational repression of hid, a microRNA target gene, known to be repressed in wing discs by the bantam miRNA. Thus, the encoded proteins may function as miRNA- and/or mRNA-specific translational regulators in vivo.
authors.affiliation: Smurfit Institute of Genetics and Trinity College Institute for Neuroscience, Trinity College Dublin, Dublin-2, Ireland.
authors.forename: Anne-Marie J
authors.initials: AM
authors.lastname: Cziko
authors.forename: Cathal T
authors.initials: CT
authors.lastname: McCann
authors.forename: Iris C
authors.initials: IC
authors.lastname: Howlett
authors.forename: Scott A
authors.initials: SA
authors.lastname: Barbee
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Duncan
authors.forename: Rene
authors.initials: R
authors.lastname: Luedemann
authors.forename: Daniela
authors.initials: D
authors.lastname: Zarnescu
authors.forename: Konrad E
authors.initials: KE
authors.lastname: Zinsmaier
authors.forename: Roy R
authors.initials: RR
authors.lastname: Parker
authors.forename: Mani
authors.initials: M
authors.lastname: Ramaswami
mesh_terms: D000483:Alleles; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology*; D005123:Eye / Q000473:pathology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism*; D012261:Ribonucleoproteins
chemical_list: D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D035683:MicroRNAs; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C467328:FMR1 protein, Drosophila; C026452:messenger ribonucleoprotein