Human Molecular Genetics, Vol 5, 1083-1091, Copyright © 1996 by Oxford University Press
DE Eberhart, HE Malter, Y Feng and ST Warren
Fragile X syndrome is a frequent cause of mental retardation resulting from
the absence of FMRP, the protein encoded by the FMR1 gene. FMRP is an
RNA-binding protein of unknown function which is associated with ribosomes.
To gain insight into FMRP function, we performed immunolocalization
analysis of FMRP truncation and fusion constructs which revealed a nuclear
localization signal (NLS) in the amino terminus of FMRP as well as a
nuclear export signal (NES) encoded by exon 14. A 17 amino acid peptide
containing the FMRP NES, which closely resembles the NES motifs recently
described for HIV-1 Rev and PKI, is sufficient to direct nuclear export of
a microinjected protein conjugate. Sucrose gradient analysis shows that
FMRP ribosome association is RNA-dependent and FMRP is found in
ribonucleoprotein (RNP) particles following EDTA treatment. These data are
consistent with nascent FMRP entering the nucleus to assemble into mRNP
particles prior to export back into the cytoplasm and suggests that fragile
X syndrome may result from altered translation of transcripts which
normally bind to FMRP.
ARTICLES
The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals
Howard Hughes Medical Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
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I. J. Weiler, S. A. Irwin, A. Y. Klintsova, C. M. Spencer, A. D. Brazelton, K. Miyashiro, T. A. Comery, B. Patel, J. Eberwine, and W. T. Greenough Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation PNAS, May 13, 1997; 94(10): 5395 - 5400. [Abstract] [Full Text] [PDF]
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Y. Feng, C.-A. Gutekunst, D. E. Eberhart, H. Yi, S. T. Warren, and S. M. Hersch Fragile X Mental Retardation Protein: Nucleocytoplasmic Shuttling and Association with Somatodendritic Ribosomes J. Neurosci., March 1, 1997; 17(5): 1539 - 1547. [Abstract] [Full Text] [PDF]
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A. Schenck, B. Bardoni, A. Moro, C. Bagni, and J.-L. Mandel A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P PNAS, July 17, 2001; 98(15): 8844 - 8849. [Abstract] [Full Text] [PDF]
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