Purified Recombinant Fmrp Exhibits Selective RNA Binding as an Intrinsic Property of the Fragile X Mental Retardation Protein*

Fragile X syndrome is caused by the transcriptional silencing of the FMR1 gene due to a trinucleotide repeat expansion. The encoded protein, Fmrp, has been found to be a nucleocytoplasmic RNA-binding protein contain-ing both KH domains and RGG boxes that associates with polyribosomes as a ribonucleoprotein particle. RNA binding has previously been demonstrated with in vitro-translated Fmrp; however, it remained uncertain whether the selective RNA binding observed was an intrinsic property of Fmrp or required an associated protein(s). Here, baculovirus-expressed and affinity-pu-rified FLAG-tagged murine Fmrp was shown to bind directly to both ribonucleotide homopolymers and hu-man brain mRNA. FLAG-Fmrp exhibited selectivity for binding poly(G)> poly(U)>> poly(C) or poly(A). More