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Molecular and Cellular Biology, November 2000, p. 8536-8547, Vol. 20, No. 22
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Characterization of dFMR1, a Drosophila melanogaster Homolog of the Fragile X Mental Retardation Protein

Lili Wan,1,2 Thomas C. Dockendorff,3 Thomas A. Jongens,3 and Gideon Dreyfuss1,2,*

Howard Hughes Medical Institute1 and Departments of Biochemistry & Biophysics2 and Genetics,3 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148

Received 1 May 2000/Returned for modification 23 June 2000/Accepted 15 August 2000

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.

* Corresponding author. Mailing address: Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148. Phone: (215) 898-0172. Fax: (215) 573-2000. E-mail: gdreyfuss{at}hhmi.upenn.edu.

Molecular and Cellular Biology, November 2000, p. 8536-8547, Vol. 20, No. 22
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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