Reduced mRNA for G3BP in fragile X cells: Evidence of FMR1 gene regulation

Although fragile X syndrome is caused by the absence of fragile X gene expr ession, little is known about the pathogenic processes underlying the menta l retardation, Recent findings that the fragile X protein, FMRP, contains R NA binding motifs and nuclear transport signals and associates with ribosom es suggest that FMRP may be involved in either mRNA processing, transport, or translation. To test the hypothesis that absence of FMRP may affect the processing of specific transcripts, me have used an RNA differential displa y assay (RDDA) to identify differentially expressed transcripts in lymphobl ast lines derived from fragile X syndrome patients. A 0.9-kb cDNA fragment that showed reduced expression in a fragile X lymphoblast cell line was fou nd to be identical to G3BP (Ras-GTPase-Activating protein SH3-domain-bindin g protein). Quantitative reverse transcriptase-polymerase chain reaction sh owed that the expressed levels of G3BP mRNA in fragile X lymphoblast cell l ines were significantly less than controls, Our results indicate that G3BP mRNA may be regulated by FMRP and supports the hypothesis that FMRP may mod ulate the transcription of specific transcripts. (C) 1999 Wiley-Liss, Inc.