The fragile X mental retardation protein is associated with ribosomes

Fragile X mental retardation syndrome is one of the most common human genetic diseases. Patients carry a methylated expansion of a CGG repeat resulting in the silencing of the FMR1 gene that codes for a heterogeneous set of proteins (FMRP). FMRP is abundant in neurons and is also widely expressed, albeit at different levels, in various human and mouse tissues. FMRP is cytoplasmic and contains two conserved RNA-binding domains, suggesting a possible involvement in RNA metabolism. However, its function remains unknown. To understand the possible role(s) of FMRP in cellular processes, we investigated its association with cellular structures. We observed that FMRP cosediments with polyribosomes after ultracentrifugation in sucrose density gradients. Following the dissociation of ribosomes into their components, we found that FMRP is associated with the ribosomal 60S subunit and possesses the characteristics of a nonintegral ribosomal protein. Immunofluorescence studies reveal a tight colocalisation of FMRP with cytoplasmic ribosomes in NIH 3T3 and HeLa cells and in primary cultures of neurons, confirming our biochemical observations. We propose that fragile X mental retardation might result from defects in the translational machinery due to the absence of FMRP.