Fragile X protein controls the efficacy of mRNA transport in Drosophila neurons.
Fragile X syndrome, the most common form of inherited mental retardation is caused by mutations in the FMR1 gene. FMR1 encodes an RNA-binding protein thought to control the transport and translation of target mRNAs. While the function of FMRP in translational control has been clearly demonstrated, its role in mRNA transport and localization in neurons remains elusive. Using a genetically encoded mRNA imaging system in Drosophila we provide the first demonstration that FMRP controls mRNA transport. Live imaging of FMRP associated mRNAs show that mRNA granules are less motile and exhibit decreased directional movement in dFmr1 mutant neurons. Furthermore, Fluorescence Recovery After Photobleaching experiments show that the mobile fraction of mRNA molecules within neurites is dependent on FMRP dosage. These data support a model whereby FMRP regulates transport efficacy, by regulating the association between mRNA cargo and microtubules and suggest a new mechanism for the disease.
Estes
Patricia S
PS
Department of Molecular and Cellular Biology, University of Arizona, Tucson AZ 85721, USA.
O'Shea
Michele
M
Clasen
Sara
S
Zarnescu
Daniela C
DC
D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000166:cytology* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005123:Eye / Q000648:ultrastructure; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008954:Models, Biological; D009154:Mutation; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051304:Profilins / Q000235:genetics / Q000378:metabolism; D034443:RNA Transport / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D049452:Green Fluorescent Proteins; D051304:Profilins; D012333:RNA, Messenger; C495737:chic protein, Drosophila