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

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 los

SUBMITTER: Uchida A 

PROVIDER: S-EPMC5552277 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature