Mitochondrial biology. Replication-transcription switch in human mitochondria.
Mitochondrial biology. Replication-transcription switch in human mitochondria.
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DOI：
10.1126/science.aaa0986
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发表时间：
2015-01-30
期刊：
影响因子：
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通讯作者：
Temiakov D
中科院分区：
文献类型：
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作者：
Agaronyan K;Morozov YI;Anikin M;Temiakov D
线粒体基因组的协调复制和表达对于代谢活跃的细胞在发育的不同阶段是至关重要的。然而，复制和转录是否可以同时进行而不相互干扰，以及mtDNA拷贝数是否可以由转录机制调节，目前还不清楚。我们发现，人转录延伸因子TEFM与线粒体RNA聚合酶(MtRNAP)和新生转录本的相互作用阻止了复制引物的产生，并增加了转录处理能力，从而在复制和转录之间起到分子开关的作用，这两个过程在线粒体中似乎是相互排斥的过程。TEFM可以允许线粒体提高转录速率，从而提高呼吸和ATP的产生，而不需要复制mtDNA，而mtDNA已经在精子发生和胚胎发生的早期阶段观察到。
Coordinated replication and expression of mitochondrial genome is critical for metabolically active cells during various stages of development. However, it is not known whether replication and transcription can occur simultaneously without interfering with each other and whether mtDNA copy number can be regulated by the transcription machinery. We found that interaction of human transcription elongation factor, TEFM with mitochondrial RNA polymerase (mtRNAP) and nascent transcript prevents generation of replication primers and increases transcription processivity thereby serving as a molecular switch between replication and transcription, which appear to be mutually exclusive processes in mitochondria. TEFM may allow mitochondria to increase transcription rates and, as consequence, respiration and ATP production without the need to replicate mtDNA, which has been observed during spermatogenesis and early stages of embryogenesis.