The dynamic landscape of transcription initiation in yeast mitochondria

Nat Commun. 2020 Aug 27;11(1):4281. doi: 10.1038/s41467-020-17793-2.

Abstract

Controlling efficiency and fidelity in the early stage of mitochondrial DNA transcription is crucial for regulating cellular energy metabolism. Conformational transitions of the transcription initiation complex must be central for such control, but how the conformational dynamics progress throughout transcription initiation remains unknown. Here, we use single-molecule fluorescence resonance energy transfer techniques to examine the conformational dynamics of the transcriptional system of yeast mitochondria with single-base resolution. We show that the yeast mitochondrial transcriptional complex dynamically transitions among closed, open, and scrunched states throughout the initiation stage. Then abruptly at position +8, the dynamic states of initiation make a sharp irreversible transition to an unbent conformation with associated promoter release. Remarkably, stalled initiation complexes remain in dynamic scrunching and unscrunching states without dissociating the RNA transcript, implying the existence of backtracking transitions with possible regulatory roles. The dynamic landscape of transcription initiation suggests a kinetically driven regulation of mitochondrial transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate
  • DNA, Fungal / genetics
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • Fluorescence Resonance Energy Transfer
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Single Molecule Imaging / methods
  • Transcription Elongation, Genetic
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Initiation, Genetic*

Substances

  • DNA, Fungal
  • MTF1 protein, S cerevisiae
  • Mitochondrial Proteins
  • RNA, Fungal
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Adenosine Triphosphate
  • DNA-Directed RNA Polymerases
  • RPO41 protein, S cerevisiae