Alternative splicing in the murine and human FXR1 genes.
Fragile X syndrome results from mutations in the X-linked FMR1 gene. The most 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 interact 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 seven isoforms that differ by the presence or absence of four DNA regions. These isoforms are found at varying levels in different tissues. The structure of the murine Fxr1h gene underlying these splicing events has also been determined. Interestingly, the longest FXR1P isoform has much greater similarity 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)(n) repeat in the 5'UTR region of Fxr1h. Continuing efforts to characterize the expression patterns of FMRP family members should aid in our understanding of their functions in various cells and tissues.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
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Kirkpatrick
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McIlwain
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Nelson
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons; D051860:Fragile X Messenger Ribonucleoprotein 1; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D018076:DNA, Complementary; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012313:RNA; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C096916:FXR1 protein, human; C497684:Fmr1 protein, mouse