title: The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein.
abstract: Fragile X syndrome is one of the most common human genetic diseases and the most common cause of hereditary mental retardation. The gene that causes fragile X syndrome, FMR1, was recently identified and sequenced 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 organisms and in cells of unaffected humans, but fragile X-affected patients express little or no FMR1. These findings demonstrate that FMR1 expression 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.
authors.affiliation: Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6148.
authors.forename: H
authors.initials: H
authors.lastname: Siomi
authors.forename: M C
authors.initials: MC
authors.lastname: Siomi
authors.forename: R L
authors.initials: RL
authors.lastname: Nussbaum
authors.forename: G
authors.initials: G
authors.lastname: Dreyfuss
mesh_terms: D000595:Amino Acid Sequence; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics*; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000276:immunology; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009419:Nerve Tissue Proteins; D012313:RNA; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; C497683:FMR1 protein, human; C072074:HNRNPK protein, human