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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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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