The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif

Fragile X syndrome is caused by the absence of protein FMRP, the function o f which is still poorly understood. Previous studies have suggested that FM RP may be involved in various aspects of mRNA metabolism, including transpo rt, stability, and/or translatability. FMRP was shown to interact with a su bset of brain mRNAs as well as with its own mRNA; however, no specific RNA- binding site could be identified precisely. Here, we report the identificat ion and characterization of a specific and high affinity binding site for F MRP in the RGG-coding region of its own mRNA. This site contains a purine q uartet motif that is essential for FMRP binding and can be substituted by a heterologous quartet-forming motif. The specific binding of FMRP to its ta rget site was confirmed further in a reticulocyte lysate through its abilit y to repress translation of a reporter gene harboring the RNA target site i n the 5'-untranslated region. Our data address interesting questions concer ning the role of FMRP in the post-transcriptional control of its own gene a nd possibly other target genes.