Nuclear genetic regulation of the human mitochondrial transcriptome

被引：52

作者：

Ali, Aminah T. ^{[1
]}

Boehme, Lena ^{[1
]}

Carbajosa, Guillermo ^{[1
]}

Seitan, Vlad C. ^{[1
]}

Small, Kerrin S. ^{[2
]}

Hodgkinson, Alan ^{[1
]}

机构：

[1] Kings Coll London, Sch Basic & Med Biosci, Dept Med & Mol Genet, London, England

[2] Kings Coll London, Sch Life Course Sci, Dept Twin Res & Genet Epidemiol, London, England

来源：

ELIFE | 2019年 / 8卷

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

OXIDATIVE STRESS; GENOMIC ANALYSIS; DNA MUTATIONS; ASSOCIATION; EXPRESSION; TISSUE; DISEASE; RNAS; DIVERSITY; PATHWAYS;

D O I：

10.7554/eLife.41927

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mitochondria play important roles in cellular processes and disease, yet little is known about how the transcriptional regime of the mitochondrial genome varies across individuals and tissues. By analyzing >11,000 RNA-sequencing libraries across 36 tissue/cell types, we find considerable variation in mitochondrial-encoded gene expression along the mitochondrial transcriptome, across tissues and between individuals, highlighting the importance of cell-type specific and post-transcriptional processes in shaping mitochondrial-encoded RNA levels. Using whole-genome genetic data we identify 64 nuclear loci associated with expression levels of 14 genes encoded in the mitochondrial genome, including missense variants within genes involved in mitochondrial function (TBRG4, MTPAP and LONP1), implicating genetic mechanisms that act in trans across the two genomes. We replicate similar to 21% of associations with independent tissue-matched datasets and find genetic variants linked to these nuclear loci that are associated with cardio-metabolic phenotypes and Vitiligo, supporting a potential role for variable mitochondrial-encoded gene expression in complex disease.

引用

页数：23

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