Scientists identify the protein that switches mitochondria from reading DNA to copying it
Researchers have discovered how a single protein called TEFM controls a critical switch in mitochondria that balances gene transcription with DNA replication. The finding could inform drug development targeting mitochondrial diseases, aging, and cancer—conditions where this balance breaks down. Understanding this molecular mechanism opens new avenues for therapeutic intervention in diseases involving mitochondrial dysfunction.
Originaltitel: TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNA
<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. 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 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>