Genetic modifiers of dFMR1 encode RNA granule components in Drosophila

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 p...

Full description

Saved in:

Bibliographic Details
Published in:	Genetics (Austin) Vol. 182; no. 4; pp. 1051 - 1060
Main Authors:	Cziko, Anne-Marie J, McCann, Cathal T, Howlett, Iris C, Barbee, Scott A, Duncan, Rebecca P, Luedemann, Rene, Zarnescu, Daniela, Zinsmaier, Konrad E, Parker, Roy R, Ramaswami, Mani
Format:	Journal Article
Language:	English
Published:	United States Genetics Society of America 01-08-2009
Subjects:	Alleles Animals Biological Transport Cells, Cultured Drosophila - genetics Drosophila Proteins - genetics Drosophila Proteins - physiology Drug abuse Eye - pathology Fragile X Mental Retardation Protein - genetics Fragile X Mental Retardation Protein - physiology Investigations Mental retardation MicroRNAs - metabolism Mutation Neurological disorders Neurons - cytology Proteins Ribonucleoproteins RNA, Messenger - metabolism Scanning electron microscopy
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Communicating editor: R. Anholt Present address: Department of Biological Sciences, University of Denver, Denver, CO 80208. Corresponding author: Smurfit Institute of Genetics and Trinity College Institute for Neuroscience, Lloyd Building, Trinity College Dublin, Dublin-2, Ireland. E-mail: mani.ramaswami@tcd.ie Present address: Department of Biology, Lewis & Clark College, Portland OR 97219. Present address: Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720. Supporting information is available online at: http://www.genetics.org/cgi/content/full/genetics.109.103234/DC1.
ISSN:	1943-2631 0016-6731 1943-2631
DOI:	10.1534/genetics.109.103234