The amino terminal extension of mammalian mitochondrial RNA polymerase ensures promoter specific transcription initiation
Journal article, 2014

Mammalian mitochondrial transcription is executed by a single subunit mitochondrial RNA polymerase (Polrmt) and its two accessory factors, mitochondrial transcription factors A and B2 (Tfam and Tfb2m). Polrmt is structurally related to singlesubunit phage RNA polymerases, but it also contains a unique N-terminal extension (NTE) of unknown function. We here demonstrate that the NTE functions together with Tfam to ensure promoter-specific transcription. When the NTE is deleted, Polrmt can initiate transcription in the absence of Tfam, both from promoters and nonspecific DNA sequences. Additionally, when in presence of Tfam and a mitochondrial promoter, the NTE-deleted mutant has an even higher transcription activity than wild-type polymerase, indicating that the NTE functions as an inhibitory domain. Our studies lead to a model according to which Tfam specifically recruits wild-type Polrmt to promoter sequences, relieving the inhibitory effect of the NTE, as a first step in transcription initiation. In the second step, Tfb2m is recruited into the complex and transcription is initiated.© The Author(s) 2014. Published by Oxford University Press.

Author

Viktor Posse

University of Gothenburg

Emily Hoberg

University of Gothenburg

Anke Dierckx

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Saba Shahzad

Karolinska Institutet

Camilla Koolmeister

Karolinska Institutet

Nils-Göran Larsson

Max Planck Institute

Karolinska Institutet

Marcus Wilhelmsson

Chalmers, Chemical and Biological Engineering, Physical Chemistry

B. Martin Hällberg

Centre for Structural Systems Biology

Karolinska Institutet

European Molecular Biology Laboratory Hamburg

Claes M Gustafsson

University of Gothenburg

Nucleic Acids Research

0305-1048 (ISSN) 1362-4962 (eISSN)

Vol. 42 6 3638-3647

Areas of Advance

Nanoscience and Nanotechnology (2010-2017)

Life Science Engineering (2010-2018)

Subject Categories

Biochemistry and Molecular Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

DOI

10.1093/nar/gkt1397

PubMed

24445803

More information

Latest update

2/21/2018