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

H Siomi; M C Siomi; R L Nussbaum; G Dreyfuss

doi:10.1016/0092-8674(93)90420-u

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.

Authors

H Siomi¹, M C Siomi, R L Nussbaum, G Dreyfuss

Affiliation

¹ Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6148.

PMID: 7688265
DOI: 10.1016/0092-8674(93)90420-u

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.

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

Substances

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