Fragile X mental retardation protein interactions with human semaphorin mRNA

CHED 846

Medhavi Bole, medhavibole@gmail.com, Lakshmi Menon, menonl@duq.edu, and Mihaela Rita Mihailescu. Department of Chemistry and Biochemistry, Duquesne University, 600 Forbes Avenue, 308 Mellon Hall, Pittsburgh, PA 15282
The most common form of inherited mental retardation is the Fragile X syndrome, which is an X-linked recessive trait caused by the expansion of a trinucleotide CGG repeat in the fragile X mental retardation 1 (FMR1) gene. The fragile X mental retardation protein (FMRP) has been proposed to bind to messenger RNAs that form G quadruplex structures. One such RNA is semaphorin 3F (S3F) mRNA, which encodes for a protein involved in the guidance of growth cones during neuronal extension. S3F RNA has been proposed to interact with FMRP via the recognition of its G quadruplex structure. In this study we demonstrate that S3F RNA folds into an intramolecular parallel G quadruplex structure to which the FMRP RGG Box domain binds with high affinity and specificity, by using fluorescence, UV, circular dichroism and NMR spectroscopy.