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Structure paper

TitleStructural basis for promoter recognition and transcription factor binding and release in human mitochondria.
Journal, issue, pagesMol Cell, Vol. 85, Issue 16, Page 3123-33136.e7, Year 2025
Publish dateAug 21, 2025
AuthorsKarl Herbine / Ashok R Nayak / Angelica Zamudio-Ochoa / Dmitry Temiakov /
PubMed AbstractTranscription in human mitochondria is driven by a core apparatus consisting of a Pol A family RNA polymerase (mtRNAP), the initiation factors TFAM and TFB2M, and the elongation factor TEFM. While ...Transcription in human mitochondria is driven by a core apparatus consisting of a Pol A family RNA polymerase (mtRNAP), the initiation factors TFAM and TFB2M, and the elongation factor TEFM. While earlier structures of initiation and elongation complexes provided valuable snapshots, they represent isolated stages of a highly dynamic and multistep process. Critical aspects of mitochondrial transcription-such as DNA recognition and melting, promoter escape, and the release of initiation factors-remain poorly understood. Here, we present a series of cryoelectron microscopy (cryo-EM) structures that capture the transcription complex as it transitions from the initial open promoter complex to the processive elongation complex through intermediate stages. Our data reveal new, previously unidentified determinants of promoter specificity: the sequential disengagement of mtRNAP from TFAM and the promoter, the release of TFB2M, and the recruitment of TEFM. Together, these findings provide a detailed molecular mechanism underlying transcription in human mitochondria.
External linksMol Cell / PubMed:40712587 / PubMed Central
MethodsEM (single particle)
Resolution2.65 - 3.77 Å
Structure data

48412

9mn4

EMDB-48412, PDB-9mn4:
Structure of the human mitochondrial initially transcribing complex, IC3
Method: EM (single particle) / Resolution: 3.05 Å

48413

9mn5

EMDB-48413, PDB-9mn5:
Structure of the human mitochondrial open transcription initiation complex, IC0
Method: EM (single particle) / Resolution: 3.04 Å

48414

9mn6

EMDB-48414, PDB-9mn6:
Structure of the human mitochondrial late-stage transcription initiation complex, IC8
Method: EM (single particle) / Resolution: 2.71 Å

48415

9mn7

EMDB-48415, PDB-9mn7:
Structure of the human mitochondrial late-stage transcription initiation complex, IC8
Method: EM (single particle) / Resolution: 2.65 Å

48416

9mn8

EMDB-48416, PDB-9mn8:
Structure of the human mitochondrial transcription initiation transitional complex, TC8
Method: EM (single particle) / Resolution: 2.69 Å

48417

9mn9

EMDB-48417, PDB-9mn9:
Structure of the human mitochondrial promoter-initiated transcription elongation complex, P-EC13
Method: EM (single particle) / Resolution: 2.74 Å

48418

9mna

EMDB-48418, PDB-9mna:
Structure of the human mitochondrial promoter-initiated transcription elongation complex with TEFM, pEC9-TEFM
Method: EM (single particle) / Resolution: 3.77 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-CH1:
3'-DEOXY-CYTIDINE-5'-TRIPHOSPHATE

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsTRANSCRIPTION / Mitochondrial RNA Polymerase / Transcription Initiation complex / POLRMT / TRANSCRIPTION-DNA-RNA complex

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