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Nucleic Acids Res. 2014 Apr;42(6):4100-12. doi: 10.1093/nar/gkt1360. Epub 2014 Jan 9.

Organization of the human mitochondrial transcription initiation complex.

Author information

1
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, Cryo-Electron Microscopy Facility, New York Structural Biology Center, New York, NY 10027 and Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.

Abstract

Initiation of transcription in human mitochondria involves two factors, TFAM and TFB2M, in addition to the mitochondrial RNA polymerase, POLRMT. We have investigated the organization of the human mitochondrial transcription initiation complex on the light-strand promoter (LSP) through solution X-ray scattering, electron microscopy (EM) and biochemical studies. Our EM results demonstrate a compact organization of the initiation complex, suggesting that protein-protein interactions might help mediate initiation. We demonstrate that, in the absence of DNA, only POLRMT and TFAM form a stable interaction, albeit one with low affinity. This is consistent with the expected transient nature of the interactions necessary for initiation and implies that the promoter DNA acts as a scaffold that enables formation of the full initiation complex. Docking of known crystal structures into our EM maps results in a model for transcriptional initiation that strongly correlates with new and existing biochemical observations. Our results reveal the organization of TFAM, POLRMT and TFB2M around the LSP and represent the first structural characterization of the entire mitochondrial transcriptional initiation complex.

PMID:
24413562
PMCID:
PMC3973321
DOI:
10.1093/nar/gkt1360
[Indexed for MEDLINE]
Free PMC Article

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