1. Chromosomes and Gene Expression
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Nuclear genetic regulation of the human mitochondrial transcriptome

Research Article
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Cite this article as: eLife 2019;8:e41927 doi: 10.7554/eLife.41927

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.

Article and author information

Author details

  1. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1089-9278
  2. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7593-7533
  3. 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.
  4. 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.
  5. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4566-0005
  6. 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.
    ORCID icon "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.

Reviewing Editor

  1. Alexis Battle, John Hopkins School of Medicine, United States

Publication history

  1. Received: September 11, 2018
  2. Accepted: February 14, 2019
  3. Accepted Manuscript published: February 18, 2019 (version 1)
  4. 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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