Mitochondrial transcription termination factor 1, MTERF1, has been reported to couple rRNA gene transcription initiation with termination and is therefore thought to be a key regulator of mammalian mitochondrial ribosome biogenesis. The prevailing model is based on a series of observations published over the last two decades, but no in vivo evidence exists to show that MTERF1 regulates transcription of the heavy-strand region of mtDNA containing the rRNA genes. Here, we demonstrate that knockout of Mterf1 in mice has no effect on mitochondrial rRNA levels or mitochondrial translation. Instead, loss of Mterf1 influences transcription initiation at the light-strand promoter, resulting in a decrease of de novo transcription manifested as reduced 7S RNA levels. Based on these observations, we suggest that MTERF1 does not regulate heavy-strand transcription, but rather acts to block transcription on the opposite strand of mtDNA to prevent transcription interference at the light-strand promoter.

Background: LRPPRC regulates mitochondrial mRNA stability and was recently reported to also stimulate mammalian mtDNA transcription.Results: Altered expression of LRPPRC in mice in vivo or addition of LRPPRC to a recombinant transcription system in vitro does not affect mtDNA transcription.Conclusion: LRPPRC is not a mitochondrial transcriptional activator.Significance: LRPPRC is an essential post-transcriptional regulator of metazoan mtDNA expression.