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首页> 美国卫生研究院文献>other >NOVEL mRNA ISOFORMS OF THE SODIUM CHANNELS Nav1.2 Nav1.3 AND Nav1.7 ENCODE PREDICTED TWO-DOMAIN TRUNCATED PROTEINS
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NOVEL mRNA ISOFORMS OF THE SODIUM CHANNELS Nav1.2 Nav1.3 AND Nav1.7 ENCODE PREDICTED TWO-DOMAIN TRUNCATED PROTEINS

机译：钠通道Nav1.2Nav1.3和Nav1.7的新型mRNA同工型编码预测的两个域的截短蛋白

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摘要

The expression of voltage-gated sodium channels is regulated at multiple levels, and in this study we addressed the potential for alternative splicing of the Nav1.2, Nav1.3, Nav1.6 and Nav1.7 mRNAs. We isolated novel mRNA isoforms of Nav1.2 and Nav1.3 from adult mouse and rat dorsal root ganglia (DRG), Nav1.3 and Nav1.7 from adult mouse brain, and Nav1.7 from neonatal rat brain. These alternatively spliced isoforms introduce an additional exon (Nav1.2 exon 17A and topologically equivalent Nav1.7 exon 16A) or exon pair (Nav1.3 exons 17A and 17B) that contain an in-frame stop codon and result in predicted two-domain, truncated proteins. The mouse and rat orthologous exon sequences are highly conserved (94-100% identities), as are the paralogous Nav1.2 and Nav1.3 exons (93% identity in mouse) to which the Nav1.7 exon has only 60% identity. Previously, Nav1.3 mRNA has been shown to be upregulated in rat DRG following peripheral nerve injury, unlike the downregulation of all other sodium channel transcripts. Here we show that the expression of Nav1.3 mRNA containing exons 17A and 17B is unchanged in mouse following peripheral nerve injury (axotomy), whereas total Nav1.3 mRNA expression is upregulated by 33% (P=0.003), suggesting differential regulation of the alternatively spliced transcripts. The alternatively spliced rodent exon sequences are highly conserved in both the human and chicken genomes, with 77-89% and 72-76% identities to mouse, respectively. The widespread conservation of these sequences strongly suggests an additional level of regulation in the expression of these channels, that is also tissue-specific.
机译：电压门控钠通道的表达受到多个水平的调节，在这项研究中，我们探讨了Nav1.2，Nav1.3，Nav1.6和Nav1.7 mRNA的可变剪接的潜力。我们从成年小鼠和大鼠背根神经节（DRG）中分离出Nav1.2和Nav1.3的新型mRNA亚型，从成年小鼠脑中分离出Nav1.3和Nav1.7，从新生大鼠脑中分离出Nav1.7。这些交替剪接的同工型引入了一个额外的外显子（Nav1.2外显子17A和拓扑等效的Nav1.7外显子16A）或外显子对（Nav1.3外显子17A和17B），它们包含一个框内终止密码子并导致了预测的两个结构域，截短的蛋白质。小鼠和大鼠直系外显子序列是高度保守的（94-100％一致性），旁系Nav1.2和Nav1.3外显子（在小鼠中为93％一致性）与Nav1.7外显子仅具有60％一致性。以前，已证明在周围神经损伤后，大鼠DRG中的Nav1.3 mRNA上调，这与所有其他钠通道转录本的下调不同。在这里我们显示，在周围神经损伤（轴切）后，小鼠中含有外显子17A和17B的Na v 1.3 mRNA的表达没有变化，而总的Na v 1.3 mRNA的表达是上调33％（P = 0.003），表明交替剪接的转录本的差异调节。交替剪接的啮齿动物外显子序列在人和鸡基因组中均高度保守，与小鼠的身份分别为77-89％和72-76％。这些序列的广泛保守性强烈暗示了这些通道表达的额外调节水平，这也是组织特异性的。

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