Unexpected sequences and structures of mtDNA required for efficient transcription from the first heavy-strand promoter
- The Pennsylvaina State University, United States
- Northeastern University, United States
- The Pennsylvania State University, United States
- Mayo Clinic College of Medicine, United States
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 carboxy–terminal 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.
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Author details
Funding
National Institute of General Medical Sciences (GM075965)
- L James Maher
National Science Foundation (MCB-1243883)
- Mark C Williams
Eberly Family Chair Endowment
- Craig E Cameron
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Uchida 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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Unexpected sequences and structures of mtDNA required for efficient transcription from the first heavy-strand promoter
eLife 6:e27283.
https://doi.org/10.7554/eLife.27283
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