Transcription in human mitochondria is driven by a single-subunit, factor-dependent RNA polymerase (mtRNAP). Despite its critical role in both expression and replication of the mitochondrial genome, transcription initiation by mtRNAP remains poorly understood. Here, we report crystal structures of human mitochondrial transcription initiation complexes assembled on both light and heavy strand promoters. The structures reveal how transcription factors TFAM and TFB2M assist mtRNAP to achieve promoter-dependent initiation. TFAM tethers the N-terminal region of mtRNAP to recruit the polymerase to the promoter whereas TFB2M induces structural changes in mtRNAP to enable promoter opening and trapping of the DNA non-template strand. Structural comparisons demonstrate that the initiation mechanism in mitochondria is distinct from that in the well-studied nuclear, bacterial, or bacteriophage transcription systems but that similarities are found on the topological and conceptual level. These results provide a framework for studying the regulation of gene expression and DNA replication in mitochondria.

中文翻译：

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线粒体转录起始的结构基础。

人类线粒体中的转录由单亚基、因子依赖性 RNA 聚合酶 (mtRNAP) 驱动。尽管 mtRNAP 在线粒体基因组的表达和复制中起着关键作用，但对 mtRNAP 的转录起始仍知之甚少。在这里，我们报告了在轻链和重链启动子上组装的人类线粒体转录起始复合物的晶体结构。这些结构揭示了转录因子 TFAM 和 TFB2M 如何协助 mtRNAP 实现启动子依赖性启动。TFAM 将 mtRNAP 的 N 末端区域束缚起来以将聚合酶募集到启动子，而 TFB2M 诱导 mtRNAP 中的结构变化，以启用启动子打开和捕获 DNA 非模板链。结构比较表明，线粒体中的起始机制不同于经过充分研究的核、细菌或噬菌体转录系统中的起始机制，但在拓扑和概念水平上发现了相似之处。这些结果为研究线粒体中基因表达和 DNA 复制的调控提供了框架。