The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein

Cell. 1993 Jul 30;74(2):291-8. doi: 10.1016/0092-8674(93)90420-u.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Female
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / diagnosis*
  • Fragile X Syndrome / genetics*
  • Heterogeneous-Nuclear Ribonucleoprotein K
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Humans
  • Male
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism
  • RNA / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / immunology
  • RNA-Binding Proteins / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / immunology
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Species Specificity


  • FMR1 protein, human
  • Heterogeneous-Nuclear Ribonucleoprotein K
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Ribonucleoproteins
  • Fragile X Mental Retardation Protein
  • HNRNPK protein, human
  • RNA