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哺乳动物多聚(A)聚合酶-α mRNA 5'-非翻译区的结构提示了一种翻译调控的机制。

The structure of the 5'-untranslated region of mammalian poly(A) polymerase-alpha mRNA suggests a mechanism of translational regulation.

机构信息

Papanikolaou Research Center of Oncology, St Savvas Hospital, Athens, Greece.

出版信息

Mol Cell Biochem. 2010 Jul;340(1-2):91-6. doi: 10.1007/s11010-010-0405-x. Epub 2010 Feb 21.

DOI:10.1007/s11010-010-0405-x
PMID:20174964
Abstract

Poly(A)polymerase-alpha (PAPOLA) has been the most extensively investigated mammalian polyadenylating enzyme, mainly in regard to its multifaceted post-translational regulation. The possibility of translational regulation of this enzyme was addressed. The transcription start site was mapped and two uORFs, highly conserved among several species, were identified in the 211-bp long, GC-rich, 5' UTR of the PAPOLA mRNA. Mutation of the 5' proximal AUG resulted in increased translational efficiency of the adjacent coding sequence, whereas no significant effect was observed after mutation of the second AUG. These observations imply that translational regulation is among the conserved mechanisms regulating PAPOLA expression.

摘要

聚(A)聚合酶-α(PAPOLA)一直是研究最为广泛的哺乳动物聚腺苷酸化酶,主要是因为其多样化的翻译后调控。本文探讨了该酶的翻译调控的可能性。本文确定了 PAPOLA mRNA 的转录起始位点,并鉴定出在 211bp 长的富含 GC 的 5'UTR 中存在两个高度保守的 uORFs。5'近端 AUG 的突变导致相邻编码序列的翻译效率增加,而第二个 AUG 的突变则没有观察到显著影响。这些观察结果表明,翻译调控是调控 PAPOLA 表达的保守机制之一。

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本文引用的文献

1
Chain termination and inhibition of mammalian poly(A) polymerase by modified ATP analogues.修饰的 ATP 类似物对哺乳动物多聚(A)聚合酶的链终止和抑制。
Biochem Pharmacol. 2010 Mar 1;79(5):669-77. doi: 10.1016/j.bcp.2009.09.028. Epub 2009 Oct 6.
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Identification of novel reference genes using multiplatform expression data and their validation for quantitative gene expression analysis.利用多平台表达数据鉴定新型内参基因并对其进行定量基因表达分析验证
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Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans.
真核基因表达的调控由非翻译基因区和其他非编码元件进行。
Cell Mol Life Sci. 2012 Nov;69(21):3613-34. doi: 10.1007/s00018-012-0990-9. Epub 2012 Apr 27.
上游开放阅读框导致蛋白质表达普遍降低,且在人类中具有多态性。
Proc Natl Acad Sci U S A. 2009 May 5;106(18):7507-12. doi: 10.1073/pnas.0810916106. Epub 2009 Apr 16.
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Sumoylation regulates multiple aspects of mammalian poly(A) polymerase function.SUMO化修饰调控哺乳动物多聚腺苷酸聚合酶功能的多个方面。
Genes Dev. 2008 Feb 15;22(4):499-511. doi: 10.1101/gad.1628208.
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3' end mRNA processing: molecular mechanisms and implications for health and disease.3' 端mRNA加工:分子机制及其对健康与疾病的影响
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6
ERK is a novel regulatory kinase for poly(A) polymerase.细胞外信号调节激酶是聚腺苷酸聚合酶的一种新型调节激酶。
Nucleic Acids Res. 2008 Feb;36(3):803-13. doi: 10.1093/nar/gkm1091. Epub 2007 Dec 15.
7
Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing.多种组蛋白去乙酰化酶和CREB结合蛋白调节前体mRNA 3'末端加工。
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Downstream control of upstream open reading frames.上游开放阅读框的下游调控
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