title: 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.
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors.forename: Mügen
authors.initials: M
authors.lastname: Terzioglu
authors.forename: Benedetta
authors.initials: B
authors.lastname: Ruzzenente
authors.forename: Julia
authors.initials: J
authors.lastname: Harmel
authors.forename: Arnaud
authors.initials: A
authors.lastname: Mourier
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Jemt
authors.forename: Marcela Dávila
authors.initials: MD
authors.lastname: López
authors.forename: Christian
authors.initials: C
authors.lastname: Kukat
authors.forename: James B
authors.initials: JB
authors.lastname: Stewart
authors.forename: Rolf
authors.initials: R
authors.lastname: Wibom
authors.forename: Caroline
authors.initials: C
authors.lastname: Meharg
authors.forename: Bianca
authors.initials: B
authors.lastname: Habermann
authors.forename: Maria
authors.initials: M
authors.lastname: Falkenberg
authors.forename: Claes M
authors.initials: CM
authors.lastname: Gustafsson
authors.forename: Chan Bae
authors.initials: CB
authors.lastname: Park
authors.forename: Nils-Göran
authors.initials: NG
authors.lastname: Larsson
mesh_terms: D000818:Animals; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012335:RNA, Ribosomal / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D061785:Transcription Initiation, Genetic
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012335:RNA, Ribosomal; D014157:Transcription Factors; C495174:mTERF protein, mouse; D012343:RNA, Transfer