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Molecular and Cellular Biology, November 2000, p. 8536-8547, Vol. 20, No. 22
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.
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
*
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.
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