Nuclear genetic regulation of the human mitochondrial transcriptome
- King's College London, United Kingdom
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
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Nuclear Genetic Regulation of the Human Mitochondrial TranscriptomeNCBI Gene Expression Omnibus, GSE125013.
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Gene-gene and gene-environment interactions detected by transcriptome sequence analysis in twinsEuropean Genome-Phenome Archive, EGAS00001000805.
Article and author information
Author details
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.
Reviewing Editor
- Alexis Battle, John Hopkins School of Medicine, United States
Publication history
- Received: September 11, 2018
- Accepted: February 14, 2019
- Accepted Manuscript published: February 18, 2019 (version 1)
- Version of Record published: March 15, 2019 (version 2)
Copyright
© 2019, Ali et al.
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.
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Nuclear genetic regulation of the human mitochondrial transcriptome
eLife 8:e41927.
https://doi.org/10.7554/eLife.41927
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