The disease gene of fragile X syndrome, FMR1 gene, encodes fragile X mental retardation protein\n(FMRP). The alternative splicing (AS) of FMR1 can affect the structure and function of FMRP. However, the biological\nfunctions of alternatively spliced isoforms remain elusive. In a previous study, we identified a new 140bp exon from\nthe intron 9 of human FMR1 gene. In this study, we further examined the biological functions of this new exon and\nits underlying signaling pathways.\nResults: qRT-PCR results showed that this novel exon is commonly expressed in the peripheral blood of normal\nindividuals. Comparative genomics showed that sequences paralogous to the 140 bp sequence only exist in the\ngenomes of primates. To explore the biological functions of the new transcript, we constructed recombinant eukaryotic\nexpression vectors and lentiviral overexpression vectors. Results showed that the spliced transcript encoded a truncated\nprotein which was expressed mainly in the cell nucleus. Additionally, several genes, including the BEX1 gene involved in\nmGluR-LTP or mGluR-LTD signaling pathways were significantly influenced when the truncated FMRP was overexpressed.\nConclusions: our work identified a new exon from amid intron 9 of human FMR1 gene with wide expression in normal\nhealthy individuals, which emphasizes the notion that the AS of FMR1 gene is complex and may in a large part account\nfor the multiple functions of FMRP.
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