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Structural basis of mitochondrial transcription
Open accessAbstract
The mitochondrial genome is transcribed by a single-subunit DNA-dependent RNA polymerase (mtRNAP) and its auxiliary factors. Structural studies have elucidated how mtRNAP cooperates with its dedicated transcription factors to direct RNA synthesis: initiation factors TFAM and TFB2M assist in promoter-DNA binding and opening by mtRNAP while the elongation factor TEFM increases polymerase processivity to the levels required for synthesis of long polycistronic mtRNA transcripts. Here, we review the emerging body of structural and functional studies of human mitochondrial transcription, provide a molecular movie that can be used for teaching purposes and discuss the open questions to guide future directions of investigation.
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“TFAM is essential for mtDNA genome maintenance and initiates mitochondrial transcription by recruiting mitochondrial RNA polymerase (POLRMT) and mitochondrial transcription factor B (TFBM) to specific promoter regions on mtDNA (Hillen et al, 2017; Hillen et al, 2018).”
From The mitochondrial long non-coding RNA lncMtloop regulates mitochondrial transcription and suppresses Alzheimer’s disease (2024) · cites this paper as Hillen et al, 2018
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Cites
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Self-citationMaintenance and Expression of Mammalian Mitochondrial DNA
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Liu, R., Xi, W., Sun, Y., Hou, Y., Wang, Y., Fu, Z., Chen, L., & Chen, X. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5778563
Additional file 3 of Identification of TEFM as a potential therapeutic target for LUAD treatment
Hu, W., Yang, J., Hu, K., Luo, G., Chen, Z., Lu, Z., Li, Y., Lv, X., Zhao, J., & Xu, C. (2024) · Figshare · doi:10.6084/m9.figshare.26755399
Additional file 2 of Identification of TEFM as a potential therapeutic target for LUAD treatment
Hu, W., Yang, J., Hu, K., Luo, G., Chen, Z., Lu, Z., Li, Y., Lv, X., zhao, J., & Xu, C. (2024) · Figshare · doi:10.6084/m9.figshare.26402031
Additional file 1 of Identification of TEFM as a potential therapeutic target for LUAD treatment
Hu, W., Yang, J., Hu, K., Luo, G., Chen, Z., Lu, Z., Li, Y., Lv, X., Zhao, J., & Xu, C. (2024) · Figshare · doi:10.6084/m9.figshare.26401810
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Jeandard, D. (2019) · theses.fr (ABES) · doi:10.70675/292f625az9431z45aaz8426z08c82f3bffa3
Ma, S., 潘秋莎, Zeng, R., Liu, Q., Yang, S., Lin, J., Liu, S., Ye, Y., Chen, R., & Li, J. (2026) · Journal of Leukocyte Biology · doi:10.1093/jleuko/qiag077
Mitochondrial RNA polyadenylation: Defining RNA fate through 3' end regulation.
Muellner-Wong, L. S., Carter, W., Freyer, C., & Wredenberg, A. (2026) · Biochimica et biophysica acta. Molecular cell research · doi:10.1016/j.bbamcr.2026.120207 · Cited by 1
do Prado, P. F. V., Sharma, S., Bhatta, A., Vučković, A. N., Marani, M. P., David, A. P. L., Kuhle, B., & Hillen, H. S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.06.749684
“This reflects a broader evolutionary trend towards divergence of mitochondrial gene expression machineries: just as mitochondrial transcription 62 and RNA processing 63,64 have evolved unique molecular solutions distinct from their bacterial ancestors and nuclear counterparts, RNA degradation in…”
Self-citationBerger, B. M., Santini, E., Manjunatha, H., Trost, L., Gerber, M., Hillen, H. S., & Ochsenreiter, T. (2026) · PLoS Biology · doi:10.1371/journal.pbio.3003945
“In human mitochondria, for instance, transcription involves four transcription factors [5,8].”
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Metadata
- Authors
- Hillen, H. S., Temiakov, D., & Cramer, P.
- Affiliations
- Max Planck Institute for Biophysical Chemistry (DE)
- Thomas Jefferson University (US)
- Corresponding author
- Hillen, Hauke S.
- Cramer, Patrick
- Venue
- Nature Structural & Molecular Biology
- Published
- 2018-09
- Volume
- 25
- Issue
- 9
- Pages
- 754-765
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC6583890
- OpenAlex
- W2890710316
- Cited by
- 111
- References
- 130
- Citations by year
- 2026: 6 · 2025: 22 · 2024: 15 · 2023: 11 · 2022: 19 · 2021: 14 · 2020: 15 · 2019: 8 · 2018: 1
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Medicine Forum (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Boehringer Ingelheim Fonds
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM104231, R01GM118941)
- 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 › Structural Biology › Enzyme Structure and Function
- Keywords
- mitochondrial transcription, mitochondrial RNA polymerase, TFAM, TFB2M, transcription factors, promoter binding, polymerase processivity, human mitochondria
- MeSH terms
- Humans, Mitochondria, Protein Conformation, Terminator Regions, Genetic, Transcription, Genetic, Evolution, Molecular, Mitochondrial Proteins, Transcriptional Elongation Factors
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