title: Mitochondrial biology. Replication-transcription switch in human mitochondria.
abstract: 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.
authors: Department of Cell Biology, School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, NJ 08084, USA.
authors: Karen
authors: K
authors: Agaronyan
authors: Department of Cell Biology, School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, NJ 08084, USA.
authors: Yaroslav I
authors: YI
authors: Morozov
authors: Department of Cell Biology, School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, NJ 08084, USA.
authors: Michael
authors: M
authors: Anikin
authors: Department of Cell Biology, School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, NJ 08084, USA. temiakdm@rowan.edu.
authors: Dmitry
authors: D
authors: Temiakov
mesh_terms: D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000378:metabolism*; D054856:G-Quadruplexes; D054629:Genome, Mitochondrial; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D008957:Models, Genetic; D008958:Models, Molecular; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D000077278:RNA, Mitochondrial; D014157:Transcription Factors / Q000378:metabolism*; D061806:Transcription Termination, Genetic; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D000077278:RNA, Mitochondrial; C560090:TEFM protein, human; D014157:Transcription Factors; D012313:RNA; D012321:DNA-Directed RNA Polymerases; C519567:POLRMT protein, human
references: Biol Reprod. 2010 Jul;83(1):52-62
references: 20130269
references: Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16072-7
references: 20798345
references: Cell Cycle. 2010 Jul 1;9(13):2537-43
references: 20581460
references: Nucleic Acids Res. 2011 May;39(10):4284-99
references: 21278163
references: Mitochondrion. 2011 Sep;11(5):797-813
references: 20933103
references: Mitochondrion. 2011 Sep;11(5):686-92
references: 21635974
references: Nucleic Acids Res. 2012 Nov 1;40(20):10334-44
references: 22965135
references: Hum Mol Genet. 2013 May 1;22(9):1867-72
references: 23390135
references: Nat Struct Mol Biol. 2013 Nov;20(11):1298-303
references: 24096365
references: Nucleic Acids Res. 2014 Apr;42(6):3884-93
references: 24393772
references: Cell Metab. 2014 Aug 5;20(2):226-40
references: 25088301
references: Cell. 2001 Nov 16;107(4):437-49
references: 11719185
references: Nature. 2002 Nov 7;420(6911):43-50
references: 12422209
references: Hum Mol Genet. 2004 May 1;13(9):935-44
references: 15016765
references: Cell. 1982 Apr;28(4):693-705
references: 6178513
references: Proc Natl Acad Sci U S A. 1985 Jan;82(2):351-5
references: 2982153
references: J Biol Chem. 1997 Jun 13;272(24):15275-9
references: 9182553
references: Nat Genet. 1999 Oct;23(2):147
references: 10508508
references: Mol Reprod Dev. 2005 Aug;71(4):405-13
references: 15895466
references: Annu Rev Genet. 2005;39:359-407
references: 16285865
references: Mol Cell. 2006 Dec 28;24(6):813-25
references: 17189185
references: Annu Rev Biochem. 2007;76:679-99
references: 17408359
references: Mol Cell. 2007 Sep 21;27(6):914-27
references: 17889665
references: Mol Cell. 2007 Dec 28;28(6):991-1001
references: 18158897
references: Mol Cell. 2010 Jan 15;37(1):67-78
references: 20129056
references: Hum Reprod. 2000 Jul;15 Suppl 2:86-91
references: 11041516