Alternative splicing in the murine and human FXR1 genes

Fragile X syndrome results from mutations in the X-linked FMR1 gene. The mo st common mutation is expansion and hypermethylation of a CGG repeat in the 5'UTR of FMR1, which blocks transcription and results in the loss of FMR1 protein (FMRP). Efforts to understand the function of FMRP have led to the identification of two autosomal homologs, FXR1P and FXR2P, that may interac t with FMRP in some tissues. Reported cDNAs for human, murine, and Xenopus FXR1 suggested the potential for alternatively spliced isoforms, a feature also found in the FMR1 gene. Using RT-PCR to characterize FXR1 alternative splicing in different mouse tissues and human cell lines, we identified sev en isoforms that differ by the presence or absence of four DNA regions. The se isoforms are found at varying levels in different tissues. The structure of the murine Fxr1h gene underlying these splicing events has also been de termined. Interestingly, the longest FXR1P isoform has much greater similar ity to FXR2P in the C-terminal region than has been previously recognized, and the gene structure of Fxr1h is quite similar to those of FMR1 and Fxr2h . However, unlike FMR1 and Fxr2h, there is no (CGG), repeat in the 5'UTR re gion of Fxr1h. Continuing efforts to characterize the expression patterns o f FMRP family members should aid in our understanding of their functions in various cells and tissues. (C) 1999 Academic Press.