MTERF1 Binds mtDNA to Prevent Transcriptional Interference at the Light-Strand Promoter but Is Dispensable for rRNA Gene Transcription Regulation

Abstract

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.

FASTKD2 is an RNA-binding protein required for mitochondrial RNA processing and translation

“…3E,F). This observation is consistent with an induction of mitochondrial transcription, a possible consequence of perturbed mitochondrial homeostasis (Metodiev et al 2009), as 7S RNA levels have previously been proposed to correlate with de novo transcriptional activity in mitochondria (Terzioglu et al 2013). Interfering with FASTKD2 expression by RNAi or CRISPR leaves TRNP steady-state levels unchanged (Fig.…”

Pathological ribonuclease H1 causes R-loop depletion and aberrant DNA segregation in mitochondria

“…Binding of a protein to TAS could arrest transcription [in the manner of mitochondrial transcription termination factor (mTERF) at another site in the mitochondrial genome (35)] and thereby prevent POLRMT progression into the CR, denying the mtDNA the first RNA needed for TDR. In the case of R-loop synthesis via the D-loop, TAS could facilitate recruitment of POLRMT or other accessory factors to the appropriate start site.…”

A Member of the Arabidopsis Mitochondrial Transcription Termination Factor Family Is Required for Maturation of Chloroplast Transfer RNAIle(GAU)

“…However, manipulation of human mTERF1 expression levels has minimal effects on steady-state levels of sensestrand transcripts (Hyvärinen et al, 2010). In vivo studies in Mterf1 knockout mice led to a model in which the major function of mTERF1 is to prevent light strand transcripts from proceeding around the mtDNA circle, thus avoiding transcriptional interference at the light strand promoter from which they originated (Terzioglu et al, 2013).…”

“…In sum, the accumulation of ribosomal subunits is reduced. Because some mammalian mTERF proteins bind to specific mtDNA sequences in vitro and in vivo (Kruse et al, 1989;Roberti et al, 1991;Daga et al, 1993;Fernandez-Silva et al, 1997;Terzioglu et al, 2013), we asked whether mTERF6 might similarly interact with plant organellar DNAs.…”

“…The assumed function of human mTERF1 as a transcription terminator (of heavy-strand transcripts) gave the whole family its name. Lately, a model has been suggested in which the major function of human mTERF1 is not termination of transcription but termination of antisense transcription to prevent light-strand transcripts from proceeding around the mitochondrial DNA (mtDNA) circle, thus avoiding transcriptional interference at the light-strand promoter from which they originated (Terzioglu et al, 2013).…”