THE PROTEIN PRODUCT OF THE FRAGILE-X GENE, FMR1, HAS CHARACTERISTICS OF AN RNA-BINDING PROTEIN

Fragile X syndrome is one of the most common human genetic diseases an d the most common cause of hereditary mental retardation. The gene tha t causes fragile X syndrome, FMR1, was recently identified and sequenc ed and found to encode a putative protein of unknown function. Here we report that FMR1 contains two types of sequence motifs recently found in RNA-binding proteins: an RGG box and two heterogeneous nuclear RNP K homology domains. We also demonstrate that FMR1 binds RNA in vitro. Using antibodies to FMR1, we detect its expression in divergent organ isms and in cells of unaffected humans, but fragile X-affected patient s express little or no FMR1. These findings demonstrate that FMR1 expr ession is directly correlated with the fragile X syndrome and suggest that anti-FMR1 antibodies will be important for diagnosis of fragile X syndrome. Furthermore, the RNA binding activity of FMR1 opens the way to understanding the function of FMR1.