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Characterization of dFMR1, a Drosophila melanogaster homolog of the fragile X mental retardation protein.

Fragile X syndrome is the most common inherited form of mental retardation. It is caused by loss of FMR1 gene activity due to either lack of expression or expression of a mutant form of the protein. In mammals, FMR1 is a member of a small protein family that consists of FMR1, FXR1, and FXR2. All three members bind RNA and contain sequence motifs that are commonly found in RNA-binding proteins, including two KH domains and an RGG box. The FMR1/FXR proteins also contain a 60S ribosomal subunit interaction domain and a protein-protein interaction domain which mediates homomer and heteromer formation with each family member. Nevertheless, the specific molecular functions of FMR1/FXR proteins are unknown. Here we report the cloning and characterization of a Drosophila melanogaster homolog of the mammalian FMR1/FXR gene family. This first invertebrate homolog, termed dfmr1, has a high degree of amino acid sequence identity/similarity with the defined functional domains of the FMR1/FXR proteins. The dfmr1 product binds RNA and is similar in subcellular localization and embryonic expression pattern to the mammalian FMR1/FXR proteins. Overexpression of dfmr1 driven by the UAS-GAL4 system leads to apoptotic cell loss in all adult Drosophila tissues examined. This phenotype is dependent on the activity of the KH domains. The ability to induce a dominant phenotype by overexpressing dfmr1 opens the possibility of using genetic approaches in Drosophila to identify the pathways in which the FMR1/FXR proteins function.

Pubmed ID: 11046149


  • Wan L
  • Dockendorff TC
  • Jongens TA
  • Dreyfuss G


Molecular and cellular biology

Publication Data

November 19, 2000

Associated Grants


Mesh Terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Antibodies, Monoclonal
  • Apoptosis
  • Cloning, Molecular
  • Drosophila melanogaster
  • Embryo, Nonmammalian
  • Fragile X Mental Retardation Protein
  • Gene Expression Regulation, Developmental
  • Genes, Dominant
  • Insect Proteins
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • RNA
  • RNA-Binding Proteins
  • Sequence Homology, Amino Acid