Nuclear genetic regulation of the human mitochondrial transcriptome.

Abstract:

: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 ~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.

journal_name

Elife

journal_title

eLife

authors

Ali AT,Boehme L,Carbajosa G,Seitan VC,Small KS,Hodgkinson A

doi

10.7554/eLife.41927

subject

Has Abstract

pub_date

2019-02-18 00:00:00

issn

2050-084X

pii

41927

journal_volume

8

pub_type

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