Genetic Modifiers of dFMR1 Encode RNA Granule Components in Drosophila
Anne-Marie J. Cziko, Cathal T. McCann, Iris C. Howlett, Scott A. Barbee, Rebecca P. Duncan, Rene Luedemann, Daniela Zarnescu, Konrad E. Zinsmaier, Roy R. Parker, Mani Ramaswami

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.

Footnotes

  • Supporting information is available online at: http://www.genetics.org/cgi/content/full/genetics.109.103234/DC1.

  • 1 Present address: Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720.

  • 2 Present address: Department of Biological Sciences, University of Denver, Denver, CO 80208.

  • 3 Present address: Department of Biology, Lewis & Clark College, Portland OR 97219.

  • Communicating editor: R. Anholt

  • Received March 25, 2009.
  • Accepted May 28, 2009.
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