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Cited by 192Genomics and Chromatin DynamicsMitochondrial Function and PathologyEnzyme Structure and Function

Structural Basis of Mitochondrial Transcription Initiation

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Hillen, Hauke S., Morozov, Yaroslav I., Sarfallah, Azadeh, Temiakov, Dmitry, Cramer, Patrick·2017·Cell
DOI 10.1016/j.cell.2017.10.036PMC PMC6590061
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Abstract

Transcription in human mitochondria is driven by a single-subunit, factor-dependent RNA polymerase (mtRNAP). Despite its critical role in both expression and replication of the mitochondrial genome, transcription initiation by mtRNAP remains poorly understood. Here, we report crystal structures of human mitochondrial transcription initiation complexes assembled on both light and heavy strand promoters. The structures reveal how transcription factors TFAM and TFB2M assist mtRNAP to achieve promoter-dependent initiation. TFAM tethers the N-terminal region of mtRNAP to recruit the polymerase to the promoter whereas TFB2M induces structural changes in mtRNAP to enable promoter opening and trapping of the DNA non-template strand. Structural comparisons demonstrate that the initiation mechanism in mitochondria is distinct from that in the well-studied nuclear, bacterial, or bacteriophage transcription systems but that similarities are found on the topological and conceptual level. These results provide a framework for studying the regulation of gene expression and DNA replication in mitochondria.

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  • TFAM is essential for mtDNA genome maintenance and initiates mitochondrial transcription by recruiting POLRMT and TFB2M to specific promoter regions on mtDNA.

    “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, 2017

    The Results section, “TFAM recruits mtRNAP to promoter DNA” (page unavailable), supports TFAM’s recruitment of POLRMT to mitochondrial promoters. The Results section, “IC structure reveals locations of TFAM, TFB2M, and DNA on mtRNAP” (page unavailable), says TFAM does not contact TFB2M, so it does not support recruitment of TFB2M by TFAM. The Introduction links transcription initiation to mitochondrial maintenance but does not establish that TFAM is essential for mtDNA genome maintenance. (LLM, conf=0.88)

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Authors
Hillen, H. S., Morozov, Y. I., Sarfallah, A., Temiakov, D., & Cramer, P.
Affiliations
  • Max Planck Institute for Biophysical Chemistry (DE)
  • Rowan University (US)
Corresponding author
  • Temiakov, Dmitry
  • Cramer, Patrick
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2017-11
Volume
171
Issue
5
Pages
1072-1081.e10
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2017.10.036
PMC
PMC6590061
OpenAlex
W2769954814
Cited by
192
References
53
Citations by year
2026: 21 · 2025: 18 · 2024: 21 · 2023: 32 · 2022: 29 · 2021: 19 · 2020: 20 · 2019: 16 · 2018: 16
FWCI
5.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Rowan Digitals Works (Rowan University) (submittedVersion, cc-by-nc-nd)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion)
  • Max Planck Digital Library (submittedVersion)
  • GRO (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • Boehringer Ingelheim Fonds
  • Deutsche Forschungsgemeinschaft (SFB860, SPP1935)
  • European Research Council (693023)
  • NIH (RO1 GM104231)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
mitochondrial RNA polymerase, TFAM, TFB2M, transcription initiation complex, promoter opening, mitochondrial genome, crystal structure, transcription factors
MeSH terms
Amino Acid Sequence, DNA-Binding Proteins, DNA, Mitochondrial, Gene Expression Regulation, Humans, Methyltransferases, Mitochondria, Models, Molecular, Promoter Regions, Genetic, DNA-Directed RNA Polymerases, Transcription Factors, Transcription, Genetic, Sequence Alignment, Bacteriophage T7, Mitochondrial Proteins, Multiprotein Complexes, Transcription Initiation, Genetic

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