THE FRAGILE-X MENTAL-RETARDATION PROTEIN IS ASSOCIATED WITH POLY(A)(-RNA IN ACTIVELY TRANSLATING POLYRIBOSOMES() MESSENGER)

The fragile X syndrome results from a transcriptional silencing of the FMR1 gene and the absence of its encoded protein. FMRP is a cytoplasm ic RNA-binding protein, whose specific cellular function is still unkn own. We present evidence that virtually all detectable cytoplasmic FMR P in mouse NIH 3T3 and human HeLa cells is found strictly in associati on with mRNA in actively translating polyribosomes, Furthermore, FMRP released from polyribosomes is associated with ribonucleoprotein compl exes with sedimentation coefficients of 60-70S and selection on oligo( dT)-cellulose reveals that this association is specific to poly(A)-con taining mRNPs, This association with actively translating polyribosome s is not affected by alteration of translational processes induced by serum stimulation and starvation in NIH 3T3 cells, suggesting that FMR 1 expression is not cell cycle regulated and that FMRP might have a ho use-keeping function, FXR2 protein, which is closely related to FMRP, is also detected associated with mRNPs in translating polyribosomes. T he results strongly suggest that FMRP might be a mRNA chaperone intera cting with mRNP complexes.