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 C Zarnescu, Konrad E Zinsmaier, Roy R. Parker, Mani Ramaswami

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1051-1060
Number of pages10
JournalGenetics
Volume182
Issue number4
DOIs
StatePublished - Aug 2009

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MicroRNAs
Drosophila
Protein Biosynthesis
RNA
Fragile X Mental Retardation Protein
Proteins
Neuronal Plasticity
Neurites
Genes
Phenotype
Neurons
Messenger RNA
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

Cziko, A. M. J., McCann, C. T., Howlett, I. C., Barbee, S. A., Duncan, R. P., Luedemann, R., ... Ramaswami, M. (2009). Genetic modifiers of dFMR1 encode RNA granule components in Drosophila. Genetics, 182(4), 1051-1060. https://doi.org/10.1534/genetics.109.103234

Genetic modifiers of dFMR1 encode RNA granule components in Drosophila. / Cziko, Anne Marie J; McCann, Cathal T.; Howlett, Iris C.; Barbee, Scott A.; Duncan, Rebecca P.; Luedemann, Rene; Zarnescu, Daniela C; Zinsmaier, Konrad E; Parker, Roy R.; Ramaswami, Mani.

In: Genetics, Vol. 182, No. 4, 08.2009, p. 1051-1060.

Research output: Contribution to journalArticle

Cziko, AMJ, McCann, CT, Howlett, IC, Barbee, SA, Duncan, RP, Luedemann, R, Zarnescu, DC, Zinsmaier, KE, Parker, RR & Ramaswami, M 2009, 'Genetic modifiers of dFMR1 encode RNA granule components in Drosophila', Genetics, vol. 182, no. 4, pp. 1051-1060. https://doi.org/10.1534/genetics.109.103234
Cziko AMJ, McCann CT, Howlett IC, Barbee SA, Duncan RP, Luedemann R et al. Genetic modifiers of dFMR1 encode RNA granule components in Drosophila. Genetics. 2009 Aug;182(4):1051-1060. https://doi.org/10.1534/genetics.109.103234
Cziko, Anne Marie J ; McCann, Cathal T. ; Howlett, Iris C. ; Barbee, Scott A. ; Duncan, Rebecca P. ; Luedemann, Rene ; Zarnescu, Daniela C ; Zinsmaier, Konrad E ; Parker, Roy R. ; Ramaswami, Mani. / Genetic modifiers of dFMR1 encode RNA granule components in Drosophila. In: Genetics. 2009 ; Vol. 182, No. 4. pp. 1051-1060.
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