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Role of the 3 untranslated region in the regulation of cytosolic glutathione peroxidase and phospholipid-hydroperoxide glutathione peroxidase gene expression by selenium supply.

机译:3非翻译区在通过供应硒调节细胞质谷胱甘肽过氧化物酶和磷脂-氢过氧化物谷胱甘肽过氧化物酶基因表达中的作用。

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摘要

Selenium is an essential nutrient and synthesis of selenoproteins is affected by limited selenium supply. During selenium deficiency there is a differential regulation of selenoprotein synthesis and gene expression; for example, there is a decrease in abundance of mRNA for cytosolic glutathione peroxidase (cGSH-Px) and a preservation of mRNA for phospholipid-hydroperoxide glutathione peroxidase (PHGSH-Px). This difference is not due to an alteration in the rate of transcription but might reflect differences in translation. The aim of the present work was to assess the role of cGSH-Px and PHGSH-Px 3' untranslated regions (UTRs) in the regulation of selenoprotein mRNA stability and translation by using H4-II-E-C3 cells transfected with different constructs containing a type I iodothyronine deiodinase-coding region linked to different selenoprotein mRNA 3' UTRs. Translational efficiency results showed that the efficiency of the 3' UTRs in permitting selenocysteine incorporation is similar in selenium-replete conditions but, when selenium is limiting, the 3' UTR of cGSH-Px is less efficient than the 3' UTR of PHGSH-Px. The results suggest that the 3' UTR of these selenoprotein mRNA species influences their extent of translation when selenium levels are low. The different sensitivity of the 3' UTRs to selenium deficiency can explain the differential effect that selenium deficiency has on cGSH-Px and PHGSH-Px activity and mRNA levels, stability and translation. This might be partly responsible for channelling selenium for synthesis of PHGSH-Px rather than cGSH-Px.
机译:硒是必不可少的营养素,硒供应有限会影响硒蛋白的合成。在硒缺乏期间,硒蛋白的合成和基因表达有不同的调节。例如,胞质谷胱甘肽过氧化物酶(cGSH-Px)的mRNA含量降低,而磷脂氢过氧化物谷胱甘肽过氧化物酶(PHGSH-Px)的mRNA含量则保持不变。这种差异不是由于转录速率的改变,而是可能反映了翻译的差异。本工作的目的是通过使用转染了不同构建体的H4-II-E-C3细胞来评估cGSH-Px和PHGSH-Px 3'非翻译区(UTR)在硒蛋白mRNA稳定性和翻译调控中的作用。 I型碘甲状腺素脱碘酶编码区,与不同的硒蛋白mRNA 3'UTR连接。翻译效率结果表明,在硒充足的条件下,允许3'UTRs允许硒代半胱氨酸掺入的效率相似,但是,当硒受到限制时,cGSH-Px的3'UTR比PHGSH-Px的3'UTR效率低。 。结果表明,当硒水平低时,这些硒蛋白mRNA种类的3'UTR会影响其翻译程度。 3'UTR对硒缺乏的不同敏感性可以解释硒缺乏对cGSH-Px和PHGSH-Px活性以及mRNA水平,稳定性和翻译的不同影响。这可能部分负责引导硒通道合成PHGSH-Px而不是cGSH-Px。

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