Alternative 5' untranslated regions are involved in expression regulation of human heme oxygenase-1.
Alternative 5' untranslated regions are involved in expression regulation of human heme oxygenase-1.
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DOI：
10.1371/journal.pone.0077224
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bauer M
中科院分区：
文献类型：
--
作者：
Kramer M;Sponholz C;Slaba M;Wissuwa B;Claus RA;Menzel U;Huse K;Platzer M;Bauer M
编码血红素加氧酶-1 (HMOX1) 的人类基因中的单核苷酸多态性 rs2071746 和 (GT)n 微卫星与多种疾病的发病率或结果相关。大多数这些关联涉及血红素的释放或氧化应激。两种多态性都位于启动子区域，但之前报道的与血红素加氧酶 1 表达的相关性仍然不一致。这种模糊性表明 5' 基因区域的组织更加复杂，我们试图对此进行更全面的研究。我们评估了 HMOX1 的 5' 末端，发现了一个新的第一个外显子 1a，将先前报道的两个多态性分别置于 5' 非翻译区域内的内含子或外显子位置。外显子 1a 的表达可在 HepG2 肝癌细胞中被氯高铁血红素诱导，并且如荧光素酶报告基因检测所示，它是血红素加氧酶-1 翻译的抑制因子。此外，小基因方法表明，5’非翻译区域内选择性剪接的定量结果受到 (GT)n 微卫星的影响。该数据支持扩展的 HMOX1 基因模型，并为血红素加氧酶 1 的表达调控提供了进一步的见解。 HMOX1 5' 非翻译区内的选择性剪接有助于翻译调节，并且是涉及遗传变异、血红素加氧酶-1 表达和疾病结果之间相互作用的机制特征。
The single nucleotide polymorphism rs2071746 and a (GT)n microsatellite within the human gene encoding heme oxygenase-1 (HMOX1) are associated with incidence or outcome in a variety of diseases. Most of these associations involve either release of heme or oxidative stress. Both polymorphisms are localized in the promoter region, but previously reported correlations with heme oxygenase-1 expression remain not coherent. This ambiguity suggests a more complex organization of the 5’ gene region which we sought to investigate more fully. We evaluated the 5‘ end of HMOX1 and found a novel first exon 1a placing the two previously reported polymorphisms in intronic or exonic positions within the 5’ untranslated region respectively. Expression of exon 1a can be induced in HepG2 hepatoma cells by hemin and is a repressor of heme oxygenase-1 translation as shown by luciferase reporter assays. Moreover, minigene approaches revealed that the quantitative outcome of alternative splicing within the 5’ untranslated region is affected by the (GT)n microsatellite. This data supporting an extended HMOX1 gene model and provide further insights into expression regulation of heme oxygenase-1. Alternative splicing within the HMOX1 5' untranslated region contributes to translational regulation and is a mechanistic feature involved in the interplay between genetic variations, heme oxygenase-1 expression and disease outcome.
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影响因子：
9.8
作者：
ENCODE Project Consortium
通讯作者：
ENCODE Project Consortium
影响因子：
8.8
作者：
Buis, C. I.;van der Steege, G.;Porte, R. J.
通讯作者：
Porte, R. J.
DOI：
10.1111/j.1432-1033.1989.tb14583.x
发表时间：
1989-02-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
SHIBAHARA, S;SATO, M;YOSHIDA, T
通讯作者：
YOSHIDA, T
影响因子：
38.9
作者：
Sheu, Chau-Chyun;Zhai, Rihong;Wang, Zhaoxi;Gong, Michelle N.;Tejera, Paula;Chen, Feng;Su, Li;Thompson, B. Taylor;Christiani, David C.
通讯作者：
Christiani, David C.
影响因子：
3.5
作者：
Nagasaki, H;Arita, M;Gotoh, O
通讯作者：
Gotoh, O