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首页> 外文期刊>Molecular and Cellular Biology >An Upstream Open Reading Frame and the Context of the Two AUG Codons Affect the Abundance of Mitochondrial and Nuclear RNase H1
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An Upstream Open Reading Frame and the Context of the Two AUG Codons Affect the Abundance of Mitochondrial and Nuclear RNase H1

机译：上游开放阅读框架和两个AUG密码子的上下文影响线粒体和核RNA酶H1的丰度。

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摘要

RNase H1 in mammalian cells is present in nuclei and mitochondria. Its absence in mitochondria results in embryonic lethality due to the failure to amplify mitochondrial DNA (mtDNA). Dual localization to mitochondria and nuclei results from differential translation initiation at two in-frame AUGs (M1 and M27) of a single mRNA. Here we show that expression levels of the two isoforms depend on the efficiency of translation initiation at each AUG codon and on the presence of a short upstream open reading frame (uORF) resulting in the mitochondrial isoform being about 10% as abundant as the nuclear form. Translation initiation at the M1 AUG is restricted by the uORF, while expression of the nuclear isoform requires reinitiation of ribosomes at the M27 AUG after termination of uORF translation or new initiation by ribosomes skipping the uORF and the M1 AUG. Such translational organization of RNase H1 allows tight control of expression of RNase H1 in mitochondria, where its excess or absence can lead to cell death, without affecting the expression of the nuclear RNase H1.
机译：哺乳动物细胞中的RNase H1存在于细胞核和线粒体中。由于无法扩增线粒体DNA（mtDNA），其在线粒体中的缺失会导致胚胎致死。线粒体和细胞核的双重定位是由单个mRNA的两个框内AUG（M1和M27）处的差异翻译起始引起的。在这里，我们表明两种同工型的表达水平取决于每个AUG密码子的翻译起始效率以及短的上游开放阅读框（uORF）的存在，导致线粒体同工型约为核型的10％ 。 M1 AUG的翻译起始受uORF的限制，而核异构体的表达需要uORF翻译终止后核糖体在M27 AUG处的重新起始，或由核糖体跳过uORF和M1 AUG的新起始。 RNase H1的这种翻译组织可以严格控制线粒体中RNase H1的表达，线粒体的过量或缺失会导致细胞死亡，而不会影响核RNase H1的表达。

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