Cited by 598Mitochondrial Function and PathologyGenomics and Chromatin DynamicsRNA and protein synthesis mechanisms

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Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA

Falkenberg, Maria, Gaspari, Martina, Rantanen, Anja, Trifunovic, Aleksandra, Larsson, Nils-Göran, Gustafsson, Claes M.·2002·Nature Genetics

DOI 10.1038/ng909

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Abstract

Characterization of the basic transcription machinery of mammalian mitochondrial DNA (mtDNA) is of fundamental biological interest and may also lead to therapeutic interventions for human diseases associated with mitochondrial dysfunction. Here we report that mitochondrial transcription factors B1 (TFB1M) and B2 (TFB2M) are necessary for basal transcription of mammalian mitochondrial DNA (mtDNA). Human TFB1M and TFB2M are expressed ubiquitously and can each support promoter-specific mtDNA transcription in a pure recombinant in vitro system containing mitochondrial RNA polymerase (POLRMT) and mitochondrial transcription factor A. Both TFB1M and TFB2M interact directly with POLRMT, but TFB2M is at least one order of magnitude more active in promoting transcription than TFB1M. Both factors are highly homologous to bacterial rRNA dimethyltransferases, which suggests that an RNA-modifying enzyme has been recruited during evolution to function as a mitochondrial transcription factor. The presence of two proteins that interact with mammalian POLRMT may allow flexible regulation of mtDNA gene expression in response to the complex physiological demands of mammalian metabolism.

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Sequence and organization of the human mitochondrial genome
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., et al. (1981) · Nature · doi:10.1038/290457a0 · Cited by 9,740
Mitochondrial diseases in man and mouse
Wallace, D. C. (1999) · Science · doi:10.1126/science.283.5407.1482 · Cited by 3,060
tRNA punctuation model of RNA processing in human mitochondria
Ojala, D., Montoya, J., & Attardi, G. M. (1981) · Nature · doi:10.1038/290470a0 · Cited by 2,561
Sequence and gene organization of mouse mitochondrial DNA.
Bibb, M., Etten, R. V., Wright, C. T., Walberg, M. W., & Clayton, D. A. (1981) · Cell · doi:10.1016/0092-8674(81)90300-7 · Cited by 1,619
Mitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice
Larsson, N.-G., Wang, J., Wilhelmsson, H., Oldfors, A., Rustin, P., Lewandoski, M., Barsh, G. S., & Clayton, D. A. (1998) · Nature Genetics · doi:10.1038/ng0398-231 · Cited by 1,594
Self-citation
The genetics and pathology of oxidative phosphorylation
Smeitink, J. A. M., van den Heuvel, L., & DiMauro, S. (2001) · Nature Reviews Genetics · doi:10.1038/35072063 · Cited by 733
Replication And Transcription Of Vertebrate Mitochondrial Dna
Clayton, D. A. (1991) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.07.110191.002321 · Cited by 652
Similarity of Human Mitochondrial Transcription Factor 1 to High Mobility Group Proteins
Parisi, M. A., & Clayton, D. A. (1991) · Science · doi:10.1126/science.2035027 · Cited by 548
MOLECULAR GENETIC ASPECTS OF HUMAN MITOCHONDRIAL DISORDERS
Larsson, N.-G., & Clayton, D. A. (1995) · Annual Review of Genetics · doi:10.1146/annurev.ge.29.120195.001055 · Cited by 493
Self-citation
TRANSCRIPTION OF THE MAMMALIAN MITOCHONDRIAL GENOME
Clayton, D. A. (1984) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.53.070184.003041 · Cited by 446

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Guja, K. E., Venkataraman, K., Yakubovskaya, E., Shi, H., Mejía, E., Hambardjieva, E., Karzai, A. W., & García–Díaz, M. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt547 · Cited by 24
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Background
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Gérard, M.-A., Krol, A., & Carbon, P. (2007) · Gene · doi:10.1016/j.gene.2007.07.011 · Cited by 22
A Mutation in the Yeast Mitochondrial Core RNA Polymerase, Rpo41, Confers Defects in Both Specificity Factor Interaction and Promoter Utilization
Matsunaga, M., & Jaehning, J. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307819200 · Cited by 21
Regulation of nuclear transcription by mitochondrial RNA in endothelial cells
Sriram, K., Qi, Z., Yuan, D., Malhi, N. K., Liu, X., Calandrelli, R., Luo, Y., Tapia, A., Jin, S., Shi, J., et al. (2023) · eLife · doi:10.7554/elife.86204 · Cited by 21
“…factors (TFs) such as NRF1 and TFAM, co-regulators such as PGC1 α , and the RNA polymerase POLRMT regulate mitochondrial biogenesis, mtDNA replication, and transcription ( Gleyzer et al., 2005 ; Virbasius and Scarpulla, 1994 ; Ojala et al., 1981 ; Falkenberg et al., 2002 ; Kühl et al., 2016 ).”
Background
Clinical and molecular aspects of diseases of mitochondrial DNA instability.
Mao, C.-C., & Holt, I. J. (2009) · PubMed · Cited by 20
Allostery through protein-induced DNA bubbles
Traverso, J. J., Manoranjan, V. S., Bishop, A. R., Rasmussen, K. Ø., & Voulgarakis, N. K. (2015) · Scientific Reports · doi:10.1038/srep09037 · Cited by 20
Vascular smooth muscle cell proliferation is dependent upon upregulation of mitochondrial transcription factor A (mtTFA) expression in injured rat carotid artery
Yoshida, T., Azuma, H., Aihara, K., Fujimura, M., Akaike, M., Mitsui, T., & Matsumoto, T. (2004) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2004.08.029 · Cited by 20
Can cytoplasmic donation rescue aged oocytes?
Tanaka, A., & Watanabe, S. (2018) · Reproductive Medicine and Biology · doi:10.1002/rmb2.12252 · Cited by 20
Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation
Gomes, T. M. B., Vincent, A. E., Menger, K. E., Stewart, J. B., & Nicholls, T. J. J. (2024) · Biochemical Journal · doi:10.1042/bcj20230262 · Cited by 20
High levels of mitochondrial heteroplasmy modify the development of ovine–bovine interspecies nuclear transferred embryos
Hua, S., Lu, C., Song, Y., Li, R., Liu, X., Quan, F., Wang, Y., Liu, J., Su, F., & Zhang, Y. (2011) · Reproduction Fertility and Development · doi:10.1071/rd11091 · Cited by 19
Edition of TFAM gene by CRISPR/Cas9 technology in bovine model
Souza, V. C. D. O., Moreira, G. S. A., Bressan, F. F., Mariano, C. G., Roballo, K. C. S., Charpentier, M., Concordet, J., Meirelles, F. V., & Ambrósio, C. E. (2019) · PLoS ONE · doi:10.1371/journal.pone.0213376 · Cited by 19
Targeting Mitochondrial Homeostasis: The Role of Acupuncture in Depression Treatment
Chen, H., Wu, C., Lv, Q., Li, M., & Ren, L. (2023) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s421540 · Cited by 21
“In addition to TFAM, PGC-1α-NRF-1/2 pathway also upregulates mitochondrial transcription factors B1 and B2 (TFB1M / TFB2M) and significantly enhances mtDNA transcription.(76,77) PGC-1α promotes mtDNA replication and mitochondrial biogenesis by interacting with its upstream and downstream factors.”
Background
Identification and characterization of the mitochondrial RNA polymerase and transcription factor in the fission yeast Schizosaccharomyces pombe
Jiang, H., Sun, W., Wang, Z., Zhang, J., Chen, D., & Murchie, A. I. H. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr103 · Cited by 19
Bone marrow mononuclear cell transplantation improves mitochondrial bioenergetics in the liver of cholestatic rats
de Andrade, D. C., de Carvalho, S. N., Pinheiro, D., Thole, A. A., Moura, A. S., de Carvalho, L., & Cortez, E. A. C. (2015) · Experimental Cell Research · doi:10.1016/j.yexcr.2015.05.002 · Cited by 19
Increased mitochondrial gene expression during L6 cell myogenesis is accelerated by insulin
Mikuła, M., Dzwonek, A., Hennig, E. E., & Ostrowski, J. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.02.008 · Cited by 19
Roles of Mitochondrial DNA in Energy Metabolism
Lv, J., Bhatia, M., & Wang, X. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-6674-0_6 · Cited by 19
mtDNA Chromatin-like Organization Is Gradually Established during Mammalian Embryogenesis
Marom, S., Blumberg, A., Kundaje, A. B., & Mishmar, D. (2019) · iScience · doi:10.1016/j.isci.2018.12.032 · Cited by 19
Positive Selection in Gene Regulatory Factors Suggests Adaptive Pleiotropic Changes During Human Evolution
Jovanović, V., Sarfert, M., Reyna-Blanco, C. S., Indrischek, H., Valdivia, D. I., Shelest, E., & Nowick, K. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.662239 · Cited by 23
“TFB2M is a nuclear gene that is a part of the mitochondrial transcription initiation complex, and as such it is required for basal transcription of mitochondrial DNA (Falkenberg et al., 2002) but also for replication and packaging of mtDNA and ribosome biogenesis (Bonawitz et al., 2006).”
Background
Role of insulin-like growth factor 1 (IGF1) in the regulation of mitochondrial bioenergetics in zebrafish oocytes: lessons from in vivo and in vitro investigations
Biswas, S., Ghosh, S., & Maitra, S. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1202693 · Cited by 19
“Besides, the mitochondrial transcription factor B paralogs (mtTFB1 and mtTFB2) are known to activate the transcription of human mtDNA (Falkenberg et al., 2002).”
Background
MTERF factors: a multifunction protein family
Roberti, M., Polosa, P. L., Bruni, F., Deceglie, S., Gadaleta, M. N., & Cantatore, P. (2010) · BioMolecular Concepts · doi:10.1515/bmc.2010.015 · Cited by 18
“By combining recombinant POLRMT, TFAM and TFB2M, the human basic mitochondrial transcription system has been reconstituted in vitro, which is able to support specific transcription initiation at the H- and L- strand promoters (16).”
Method
Loss of MED1 triggers mitochondrial biogenesis in C2C12 cells
Yu, J., Xiao, Y., Liu, J., Ji, Y., Liu, H., Xu, J., Jin, X., Liu, L., Guan, M., & Jiang, P. (2013) · Mitochondrion · doi:10.1016/j.mito.2013.12.004 · Cited by 18
YAF2-Mediated YY1-Sirtuin6 Interactions Responsible for Mitochondrial Downregulation in Aging Tunicates
Kawamura, K., Higuchi, T., & Fujiwara, S. (2021) · Molecular and Cellular Biology · doi:10.1128/mcb.00047-21 · Cited by 17
The Dictyostelium model for mitochondrial biology and disease
Pearce, X. G., Annesley, S. J., & Fisher, P. R. (2019) · The International Journal of Developmental Biology · doi:10.1387/ijdb.190233pf · Cited by 18
“Unlike bacteriophage mtRNAPs, eukaryotic mtRNAPs require additional proteins for efficient transcription, known as mitochondrial transcription factors (Falkenberg et al., 2002).”
Background
Dynamic regulation of mitochondrial transcription as a mechanism of cellular adaptation
Blomain, E. S., & McMahon, S. B. (2012) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2012.06.004 · Cited by 17
“However there is significant evidence since their discovery to support nonredundant functions for TFB1M and TFB2M [17-19].”
BackgroundInfluential
CHILD: a new tool for detecting low-abundance insertions and deletions in standard sequence traces
Zhidkov, I., Cohen, R., Geifman, N., Mishmar, D., & Rubin, E. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq1354 · Cited by 17
“For pMitA, PCR products of human mtDNA fragments corresponding to positions 1–722 (Revised Cambridge Reference Sequence (rCRS) NC_012920), with or without a 51-bp deletion corresponding to positions 297–348, (pMitA and pMitA 51, respectively) were amplified and cloned into the pUC18 vector, as described previously (25…”
Method
Cloning of the sea urchin mitochondrial RNA polymerase and reconstitution of the transcription termination system
Polosa, P. L., Deceglie, S., Falkenberg, M., Roberti, M., Ponzio, B. D., Gadaleta, M. N., & Cantatore, P. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm159 · Cited by 17
“To purify the isolated recombinant mtRNAP from the cells co-expressing mtRNAP and TFB1M, we used Niþ2-NTA agarose affinity chromatography followed by a further purification on Heparin–Sepharose resin (Amersham Biosciences).”
BackgroundMethodInfluentialSelf-citation
Development of a human mitochondria-focused cDNA microarray (hMitChip) and validation in skeletal muscle cells: implications for pharmaco- and mitogenomics
Alesci, S., Manoli, I., Michopoulos, V., Brouwers, F. M., Le, H., Gold, P., Blackman, M. R., Rennert, O. M., Su, Y. A., & Chrousos, G. P. (2006) · The Pharmacogenomics Journal · doi:10.1038/sj.tpj.6500377 · Cited by 17
The Transcription of Plant Organelle Genomes
Weihe, A. (2004) · Springer eBooks · doi:10.1007/978-1-4020-3166-3_8 · Cited by 19
Correction: Dysregulation of Mitochondrial Dynamics and the Muscle Transcriptome in ICU Patients Suffering from Sepsis Induced Multiple Organ Failure
Fredriksson, K., Tjäder, I., Keller, P., Petrovic, N., Ahlman, B. H. J., Scheele, C. C., Wernerman, J., Timmons, J. A., & Rooyackers, O. (2008) · PLoS ONE · doi:10.1371/annotation/68d951f9-a236-472f-98af-24e4cc4c1a20 · Cited by 17
Impaired mitochondrial biogenesis in hippocampi of rats with chronic seizures
Han, Y., Lin, Y., Xie, N., Xue, Y., Tao, H., Rui, C., Xu, J., Cao, L., Liu, X., Jiang, H., et al. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.07.068 · Cited by 16
hMTERF4 knockdown in HeLa cells results in sub-G1 cell accumulation and cell death
Yu, M., Dai, J., Huang, W., Jiao, Y., Liu, L., Wu, M., & Tan, D. (2011) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmr020 · Cited by 16
Ras-ERK-ETS inhibition alleviates neuronal mitochondrial dysfunction by reprogramming mitochondrial retrograde signaling
Duncan, O. F., Granat, L., Ranganathan, R., Singh, V. K., Mazaud, D., Fanto, M., Chambers, D. J., Ballard, C. G., & Bateman, J. M. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007567 · Cited by 17
A Historical Perspective on RNA Editing
Koslowsky, D. J. (2004) · Humana Press eBooks · doi:10.1385/1-59259-775-0:161 · Cited by 16
Transcription in Plant Mitochondria
Liere, K., & Börner, T. (2010) · Springer eBooks · doi:10.1007/978-0-387-89781-3_4 · Cited by 15
“Animals have two mitochondrial homologs of sc-mtTFB, mtTFB1 and mtTFB2 (Falkenberg et al. 2002; McCulloch et al. 2002; Rantanen et al. 2003; Matsunaga and Jaehning 2004).”
Background
Progressively disrupted somatodendritic morphology in dopamine neurons in a mouse Parkinson's model
Lynch, W. B., Tschumi, C. W., Sharpe, A. L., Branch, S. Y., Chen, C., Ge, G., Li, S., & Beckstead, M. J. (2018) · Movement Disorders · doi:10.1002/mds.27541 · Cited by 15
p62 Promotes the Mitochondrial Localization of p53 through Its UBA Domain and Participates in Regulating the Sensitivity of Ovarian Cancer Cells to Cisplatin
Kong, Q., Yan, X., Cheng, M., Jiang, X. M., Xu, L., Shen, L., Yu, H., & Sun, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063290 · Cited by 16
“The human mitochondrial DNA is transcribed by mitochondrial RNA polymerase (POLRMT) and requires two initiation factors, namely, the mitochondrial transcription factors A (TFAM) and B2 (TFB2M) to form a transcription complex [41,42].”
Background
Triplication of HSA21 on alterations in structure and function of mitochondria
Ganguly, B. B., & Kadam, N. N. (2022) · Mitochondrion · doi:10.1016/j.mito.2022.05.007 · Cited by 16
Transcriptional initiation under conditions of anoxia-induced quiescence in mitochondria fromArtemia franciscanaembryos
Eads, B. D., & Hand, S. C. (2003) · Journal of Experimental Biology · doi:10.1242/jeb.00110 · Cited by 15
Recent Developments in Mitochondrial G‐Quadruplex Recognising Fluorescent Probes: A Review
Kumar, P., Pandith, A., Tseng, C., & Burnouf, T. (2023) · Journal of Photochemistry and Photobiology C Photochemistry Reviews · doi:10.1016/j.jphotochemrev.2023.100619 · Cited by 14
Deregulation of mitochondrial gene expression in cancer: mechanisms and therapeutic opportunities
Berner, M. J., Wall, S. W., & Echeverria, G. V. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02817-1 · Cited by 14
“Four core components, POLRMT, TFAM, transcription factor B1 of the mitochondria (TFB1M) and TFB2M, are necessary and suf ﬁ cient for mammalian mitochondrial transcription [39].”
MTERF1 regulates the oxidative phosphorylation activity and cell proliferation in HeLa cells
Chen, G., Dai, J., Tan, S., Meng, S., Liu, Z., Li, M., Cui, Q., & Yu, M. (2014) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmu029 · Cited by 14
Mitochondrial matrix processes
Mazunin, I., Левицкий, С. А., Patrushev, M. V., & Kamenski, P. A. (2015) · Biochemistry (Moscow) · doi:10.1134/s0006297915110036 · Cited by 14

Authors: Falkenberg, M., Gaspari, M., Rantanen, A., Trifunovic, A., Larsson, N.-G., & Gustafsson, C. M.
Affiliations: Karolinska Institutet (SE)
Corresponding author: Larsson, Nils-Göran
Gustafsson, Claes M.
ORCID: Falkenberg, Maria
Larsson, Nils-Göran
Gustafsson, Claes M.
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2002-06-17
Volume: 31
Issue: 3
Pages: 289-294
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng909
OpenAlex: W2081360068
Cited by: 598
References: 30
Citations by year: 2026: 5 · 2025: 14 · 2024: 14 · 2023: 14 · 2022: 15 · 2021: 18 · 2020: 19 · 2019: 24 · 2018: 23 · 2017: 31 · 2016: 17 · 2015: 26 · 2014: 22 · 2013: 30 · 2012: 30
FWCI: 10.08
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords: mitochondrial transcription factors, TFB1M, TFB2M, mitochondrial transcription, mitochondrial RNA polymerase, transcriptional regulation, mitochondrial dysfunction
MeSH terms: Amino Acid Sequence, Animals, DNA-Binding Proteins, DNA, Mitochondrial, Humans, Leukocytes, Methyltransferases, Molecular Sequence Data, Promoter Regions, Genetic, Recombinant Proteins, DNA-Directed RNA Polymerases, Transcription Factors, Transcription, Genetic, Sequence Homology, Amino Acid, Mitochondrial Proteins, Mice, In Vitro Techniques

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Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA

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