Replication-transcription switch in human mitochondria

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Science  30 Jan 2015:
Vol. 347, Issue 6221, pp. 548-551
DOI: 10.1126/science.aaa0986

Switching transcription and replication

Because mitochondrial DNA is circular, the transcription and replication machinery might be expected to collide. A single mitochondrial RNA polymerase (mtRNAP) transcribes the mitochondrial DNA and also generates primers for replication. Agaronyan et al. now show that transcription and replication are kept separate in human mitochondria, with the mitochondrial transcription elongation factor TEFM serving as a key player in the switch. In the absence of TEFM, mtRNAP terminates downstream from the promoter, forming primers to promote replication. In the presence of TEFM, the primers are not formed, and the overall processivity of mtRNAP elongation complexes is enhanced, promoting genome transcription. These mutually exclusive mechanisms allow the processes to proceed independently as needed by the cell.

Science, this issue p. 548


Coordinated replication and expression of the 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 mitochondrial DNA copy number can be regulated by the transcription machinery. We found that interaction of human transcription elongation factor TEFM with mitochondrial RNA polymerase and nascent transcript prevents the generation of replication primers and increases transcription processivity and thereby serves 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 a consequence, respiration and adenosine triphosphate production without the need to replicate mitochondrial DNA, as has been observed during spermatogenesis and the early stages of embryogenesis.

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