A novel intermediate in transcription initiation by human mitochondrial RNA polymerase

Yaroslav I. Morozov, Karen Agaronyan, Alan C.M. Cheung, Michael Anikin, Patrick Cramer, Dmitry Temiakov

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

The mitochondrial genome is transcribed by a single-subunit T7 phage-like RNA polymerase (mtRNAP), structurally unrelated to cellular RNAPs. In higher eukaryotes, mtRNAP requires two transcription factors for efficient initiation-TFAM, a major nucleoid protein, and TFB2M, a transient component of mtRNAP catalytic site. The mechanisms behind assembly of the mitochondrial transcription machinery and its regulation are poorly understood. We isolated and identified a previously unknown human mitochondrial transcription intermediate- a pre-initiation complex that includes mtRNAP, TFAM and promoter DNA. Using protein- protein cross-linking, we demonstrate that human TFAM binds to the N-terminal domain of mtRNAP, which results in bending of the promoter DNA around mtRNAP. The subsequent recruitment of TFB2M induces promoter melting and formation of an open initiation complex. Our data indicate that the pre-initiation complex is likely to be an important target for transcription regulation and provide basis for further structural, biochemical and biophysical studies of mitochondrial transcription.

Original languageEnglish (US)
Pages (from-to)3884-3893
Number of pages10
JournalNucleic acids research
Volume42
Issue number6
DOIs
StatePublished - Apr 2014

All Science Journal Classification (ASJC) codes

  • Genetics

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