The gene expression of two endoplasmic reticulum aminopeptidase 1 isoforms is regulated by distinct posttranscriptional mechanisms
The gene expression of two endoplasmic reticulum aminopeptidase 1 isoforms is regulated by distinct posttranscriptional mechanisms
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两种内质网氨肽酶 1 亚型的基因表达受不同的转录后机制调节
DOI：
10.1016/j.bbrc.2018.08.117
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发表时间：
2018
影响因子：
3.1
通讯作者：
Tsujimoto Masafumi
中科院分区：
文献类型：
--
作者：
Aoki Kazuma;Furuya Akemi;Matsumoto Ken;Tsujimoto Masafumi
内质网氨肽酶1（ERAP 1）是一种多功能酶，属于M1家族的氨肽酶，并显示与各种自身免疫性疾病有关。人ERAP 1蛋白有两种异构体，它们是由3′端外显子的选择性剪接产生的，尽管它们的功能差异尚未完全阐明。在这项研究中，我们发现，异构体通过各自的3′非翻译区进行不同的转录后调控机制。使用一个报告系统，我们确定了几个顺式元件是重要的调节选择性剪接。最后，我们揭示了干扰素γ对ERAP 1基因的转录诱导与选择性剪接之间的密切关系。这些结果表明，两个ERAP 1亚型的功能在不同的病理生理条件下。
Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) is a multifunctional enzyme belonging to the M1 family of aminopeptidases and shown to be associated with various autoimmune diseases. Human ERAP1 protein has two isoforms produced by alternative splicing of the 3′ terminal exon, although their functional differences have not yet been fully clarified. In this study, we showed that the isoforms undergo different posttranscriptional regulation mechanisms via their respective 3′ untranslated regions. Using a reporter system, we identified severalcis-elements that are important for the regulation of alternative splicing. Finally, we revealed a close relationship between the transcriptional induction of theERAP1gene by interferon-gamma and the alternative splicing. These results suggest that the two ERAP1 isoforms function under different pathophysiological conditions.