The Fragile X Mental Retardation Protein Is a Ribonucleoprotein Containing Both Nuclear Localization and Nuclear Export Signals

Hum Mol Genet. 1996 Aug;5(8):1083-91. doi: 10.1093/hmg/5.8.1083.

Abstract

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.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Transport, Active
  • COS Cells
  • Cell Nucleus / metabolism
  • Exons
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism*
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Sorting Signals / chemistry
  • Protein Sorting Signals / genetics
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleoproteins / chemistry
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism
  • Ribosomes / metabolism
  • Transfection

Substances

  • FMR1 protein, human
  • Nerve Tissue Proteins
  • Protein Sorting Signals
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Ribonucleoproteins
  • messenger ribonucleoprotein
  • Fragile X Mental Retardation Protein