Nuclear genetic regulation of the human mitochondrial transcriptome

Abstract
Data availability
Article and author information
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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.

Data availability

Anonymized processed mitochondrial encoded gene expression matrices are available in supplementary file 2 and from the Gene Expression Omnibus under accession GSE125013

The following data sets were generated

1. Ali AT
2. Boehme L
3. Carbajosa G
4. Seitan VC
5. Small KS
6. Hodgkinson A
(2019) Nuclear Genetic Regulation of the Human Mitochondrial Transcriptome
NCBI Gene Expression Omnibus, GSE125013.

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE125013

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Article and author information

Author details

Aminah T Ali

Department of Medical and Molecular Genetics, King's College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1089-9278
Lena Boehme

Department of Medical and Molecular Genetics, King's College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7593-7533
Guillermo Carbajosa

Department of Medical and Molecular Genetics, King's College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Vlad C Seitan

Department of Medical and Molecular Genetics, King's College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Kerrin S Small

Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4566-0005
Alan Hodgkinson

Department of Medical and Molecular Genetics, King's College London, London, United Kingdom

For correspondence
alan.hodgkinson@kcl.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1636-491X

Funding

Medical Research Council (MR/L016311/1)

Alan Hodgkinson

Biotechnology and Biological Sciences Research Council (BB/R006075/1)

Guillermo Carbajosa
Alan Hodgkinson

People Programme of the European Union's Seventh Framework Programme (FP7/2007-2013)

Alan Hodgkinson

Generation trust

Aminah T Ali

Medical Research Council (MR/L01999X/1)

Kerrin S Small

Medical Research Council (MR/M009343/1)

Vlad C Seitan

Guy's and St. Thomas' Charity (MAJ110901)

Lena Boehme

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.