Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression

Hum Mol Genet. 2002 Nov 15;11(24):3007-17. doi: 10.1093/hmg/11.24.3007.


Absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein, is responsible for the Fragile X syndrome, the most common form of inherited mental retardation. FMRP is a cytoplasmic protein associated with mRNP complexes containing poly(A)+mRNA. As a step towards understanding FMRP function(s), we have established the immortal STEK Fmr1 KO cell line and showed by transfection assays with FMR1-expressing vectors that newly synthesized FMRP accumulates into cytoplasmic granules. These structures contain mRNAs and several other RNA-binding proteins. The formation of these cytoplasmic granules is dependent on determinants located in the RGG domain. We also provide evidence that FMRP acts as a translation repressor following co-transfection with reporter genes. The FMRP-containing mRNPs are dynamic structures that oscillate between polyribosomes and cytoplasmic granules reminiscent of the Stress Granules that contain repressed mRNAs. We speculate that, in neurons, FMRP plays a role as a mRNA repressor in incompetent mRNP granules that have to be translocated from the cell body to distal locations such as dendritic spines and synaptosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytoplasmic Granules / metabolism*
  • Fluorescent Antibody Technique
  • Gene Expression Regulation / physiology
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Polyribosomes / metabolism
  • Protein Biosynthesis / physiology*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism*


  • FXR1 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins