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

中文翻译：

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进一步鉴定人FMR1基因第9内含子140bp序列为新的外显子。

脆性X综合征的疾病基因FMR1基因编码脆性X智力低下蛋白（FMRP）。FMR1的替代拼接（AS）可能会影响FMRP的结构和功能。但是，选择性剪接的同工型的生物学功能仍然难以捉摸。在先前的研究中，我们从人FMR1基因的内含子9中鉴定出一个新的140bp外显子。在这项研究中，我们进一步检查了这个新的外显子的生物学功能及其潜在的信号传导途径。qRT-PCR结果表明，这种新的外显子通常在正常人的外周血中表达。比较基因组学表明，与140 bp序列同源的序列仅存在于灵长类动物的基因组中。要探索新转录本的生物学功能，我们构建了重组真核表达载体和慢病毒过表达载体。结果显示，剪接的转录本编码一种截短的蛋白质，其主要在细胞核中表达。此外，当截短的FMRP过表达时，包括mGluR-LTP或mGluR-LTD信号传导途径的BEX1基因在内的几个基因也受到显着影响。我们的工作从人FMR1基因的内含子9中鉴定出一个新的外显子，该外显子在正常健康个体中具有广泛的表达，这强调了FMR1基因的AS是复杂的，并且可能在很大程度上说明了FMRP的多种功能。当截短的FMRP过表达时，包括参与mGluR-LTP或mGluR-LTD信号通路的BEX1基因受到显着影响。我们的工作从人FMR1基因的第9号内含子中鉴定出一个新的外显子，该外显子在正常健康个体中具有广泛的表达，这强调了FMR1基因的AS是复杂的，并且可能在很大程度上说明了FMRP的多种功能。当截短的FMRP过表达时，包括参与mGluR-LTP或mGluR-LTD信号通路的BEX1基因受到显着影响。我们的工作从人FMR1基因的第9号内含子中鉴定出一个新的外显子，该外显子在正常健康个体中具有广泛的表达，这强调了FMR1基因的AS是复杂的，并且可能在很大程度上说明了FMRP的多种功能。