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鼠线粒体 tRNA 的组织特异性表达图谱。

Tissue-specific expression atlas of murine mitochondrial tRNAs.

机构信息

Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China; Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

出版信息

J Biol Chem. 2021 Aug;297(2):100960. doi: 10.1016/j.jbc.2021.100960. Epub 2021 Jul 13.

Abstract

Mammalian mitochondrial tRNA (mt-tRNA) plays a central role in the synthesis of the 13 subunits of the oxidative phosphorylation complex system (OXPHOS). However, many aspects of the context-dependent expression of mt-tRNAs in mammals remain unknown. To investigate the tissue-specific effects of mt-tRNAs, we performed a comprehensive analysis of mitochondrial tRNA expression across five mice tissues (brain, heart, liver, skeletal muscle, and kidney) using Northern blot analysis. Striking differences in the tissue-specific expression of 22 mt-tRNAs were observed, in some cases differing by as much as tenfold from lowest to highest expression levels among these five tissues. Overall, the heart exhibited the highest levels of mt-tRNAs, while the liver displayed markedly lower levels. Variations in the levels of mt-tRNAs showed significant correlations with total mitochondrial DNA (mtDNA) contents in these tissues. However, there were no significant differences observed in the 2-thiouridylation levels of tRNA, tRNA, and tRNA among these tissues. A wide range of aminoacylation levels for 15 mt-tRNAs occurred among these five tissues, with skeletal muscle and kidneys most notably displaying the highest and lowest tRNA aminoacylation levels, respectively. Among these tissues, there was a negative correlation between variations in mt-tRNA aminoacylation levels and corresponding variations in mitochondrial tRNA synthetases (mt-aaRS) expression levels. Furthermore, the variable levels of OXPHOS subunits, as encoded by mtDNA or nuclear genes, may reflect differences in relative functional emphasis for mitochondria in each tissue. Our findings provide new insight into the mechanism of mt-tRNA tissue-specific effects on oxidative phosphorylation.

摘要

哺乳动物线粒体 tRNA(mt-tRNA)在氧化磷酸化复合物系统(OXPHOS)的 13 个亚基的合成中起着核心作用。然而,哺乳动物中 mt-tRNA 的上下文相关表达的许多方面仍然未知。为了研究 mt-tRNA 在组织中的特异性表达,我们使用Northern blot 分析对五种小鼠组织(脑、心、肝、骨骼肌和肾)中的线粒体 tRNA 表达进行了全面分析。观察到 22 种 mt-tRNA 在组织特异性表达方面存在显著差异,在某些情况下,这五种组织中的表达水平最低和最高之间的差异高达十倍。总的来说,心脏表现出最高水平的 mt-tRNA,而肝脏则显示出明显较低的水平。mt-tRNA 水平的变化与这些组织中的总线粒体 DNA(mtDNA)含量有显著相关性。然而,在这些组织中,tRNA、tRNA 和 tRNA 的 2-硫代尿嘧啶化水平没有观察到显著差异。15 种 mt-tRNA 在这五种组织中的氨酰化水平差异很大,骨骼肌和肾脏的氨酰化水平分别最高和最低。在这些组织中,mt-tRNA 氨酰化水平的变化与相应的线粒体 tRNA 合成酶(mt-aaRS)表达水平的变化之间存在负相关。此外,OXPHOS 亚基的可变水平,由 mtDNA 或核基因编码,可能反映了线粒体在每种组织中的相对功能重点的差异。我们的研究结果为 mt-tRNA 对氧化磷酸化的组织特异性影响的机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83c6/8342785/3f2c0231c2b7/gr1.jpg

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