Fragile X mental retardation protein targets G quartet mRNAs important forneuronal function

Loss of fragile X mental retardation protein (FMRP) function causes the fra gile X mental retardation syndrome. FMRP harbors three RNA binding domains, associates with polysomes, and is thought to regulate mRNA translation and /or localization, but the RNAs to which it binds are unknown. We have used RNA selection to demonstrate that the FMRP RGG box binds intramolecular G q uartets. This data allowed us to identify mRNAs encoding proteins involved in synaptic or developmental neurobiology that harbor FMRP binding elements . The majority of these mRNAs have an altered polysome association in fragi le X patient cells. These data demonstrate that G quartets serve as physiol ogically relevant targets for FMRP and identify mRNAs whose dysregulation m ay underlie human mental retardation.