Mitochondria contain their own DNA (mtDNA) that is expressed and replicated by nucleus-encoded factors imported into the organelle. Recently, the core human mitochondrial transcription machinery has been defined, comprising a bacteriophage-related mtRNA polymerase (POLRMT), an HMG-box transcription factor (h-mtTFA), and two transcription factors (h-mtTFB1 and h-mtTFB2) that also serve as rRNA methyltransferases. Here, we describe these transcription components as well as recent insights into the mechanism of human mitochondrial transcription initiation and its regulation. We also discuss novel roles for the mitochondrial transcription machinery beyond transcription initiation, including priming of mtDNA replication, packaging of mtDNA, coordination of ribosome biogenesis, and coupling of transcription to translation.
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