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<p>Transcription of human mitochondrial DNA (mtDNA) begins from specific transcription promoters. In strand-asynchronous mtDNA replication, transcripts from the light-strand promoter serve as primers for leading-strand synthesis at the origin of the H-strand replication (O<sub>H</sub>). A 7S DNA strand, a presumed aborted replication product, is also synthesized from O<sub>H</sub>. Transition from RNA synthesis to DNA synthesis at O<sub>H</sub> is crucial for balancing replication with transcription, yet the mechanism remains unclear. Herein, we examine the role of mitochondrial transcription elongation factor (TEFM) in this process. <i>TEFM</i> knockout results in decreased 7S DNA, strand-asynchronous replication intermediates, and mtDNA copy number, all of which are concordant with downregulation of RNA-to-DNA transition at O<sub>H</sub>. Conversely, levels of tRNAs encoded near transcription promoters increase, indicating enhanced transcription initiation frequency. Taken together, we propose that, in addition to conferring processivity to the mitochondrial RNA polymerase, TEFM plays a crucial role in maintaining the balance between mitochondrial transcription and replication.</p>

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TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNA

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月8日

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  • Shigeru Matsuda,
  • Masunari Nakayama,
  • Yura Do,
  • Takashi Ishiuchi,
  • Mikako Yagi,
  • Sjoerd Wanrooij,
  • Kazuto Nakada,
  • Fan-Yan Wei,
  • Kenji Ichiyanagi,
  • Hiroyuki Sasaki,
  • Dongchon Kang,
  • Takehiro Yasukawa

摘要

Transcription of human mitochondrial DNA (mtDNA) begins from specific transcription promoters. In strand-asynchronous mtDNA replication, transcripts from the light-strand promoter serve as primers for leading-strand synthesis at the origin of the H-strand replication (OH). A 7S DNA strand, a presumed aborted replication product, is also synthesized from OH. Transition from RNA synthesis to DNA synthesis at OH is crucial for balancing replication with transcription, yet the mechanism remains unclear. Herein, we examine the role of mitochondrial transcription elongation factor (TEFM) in this process. TEFM knockout results in decreased 7S DNA, strand-asynchronous replication intermediates, and mtDNA copy number, all of which are concordant with downregulation of RNA-to-DNA transition at OH. Conversely, levels of tRNAs encoded near transcription promoters increase, indicating enhanced transcription initiation frequency. Taken together, we propose that, in addition to conferring processivity to the mitochondrial RNA polymerase, TEFM plays a crucial role in maintaining the balance between mitochondrial transcription and replication.