Unexpected sequences and structures of mtDNA required for efficient transcription from the first heavy-strand promoter

Akira Uchida, Divakaran Murugesapillai, Markus Kastner, Yao Wang, Maria F. Lodeiro, Shaan Prabhakar, Guinevere V. Oliver, Jamie J. Arnold, L. James Maher, Mark C. Williams, Craig E. Cameron

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Human mtDNA contains three promoters, suggesting a need for differential expression of the mitochondrial genome. Studies of mitochondrial transcription have used a reductionist approach, perhaps masking differential regulation. Here we evaluate transcription from light-strand (LSP) and heavy-strand (HSP1) promoters using templates that mimic their natural context. These studies reveal sequences upstream, hypervariable in the human population (HVR3), and downstream of the HSP1 transcription start site required for maximal yield. The carboxyterminal tail of TFAM is essential for activation of HSP1 but not LSP. Images of the template obtained by atomic force microscopy show that TFAM creates loops in a discrete region, the formation of which correlates with activation of HSP1; looping is lost in tail-deleted TFAM. Identification of HVR3 as a transcriptional regulatory element may contribute to between-individual variability in mitochondrial gene expression. The unique requirement of HSP1 for the TFAM tail may enable its regulation by post-translational modifications.

Original languageEnglish (US)
Article numbere27283
JournaleLife
Volume6
DOIs
StatePublished - Jul 26 2017

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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