The amino terminal extension of mammalian mitochondrial RNA polymerase ensures promoter specific transcription initiation
Artikel i vetenskaplig tidskrift, 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.

Författare

Viktor Posse

Göteborgs universitet

Emily Hoberg

Göteborgs universitet

Anke Dierckx

Chalmers, Kemi- och bioteknik, Fysikalisk kemi

Saba Shahzad

Karolinska Institutet

Camilla Koolmeister

Karolinska Institutet

Nils-Göran Larsson

Max Planck-institutet

Karolinska Institutet

Marcus Wilhelmsson

Chalmers, Kemi- och bioteknik, Fysikalisk kemi

B. Martin Hällberg

Centre for Structural Systems Biology

Karolinska Institutet

European Molecular Biology Laboratory Hamburg

Claes M Gustafsson

Göteborgs universitet

Nucleic Acids Research

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

Vol. 42 3638-3647

Styrkeområden

Nanovetenskap och nanoteknik

Livsvetenskaper och teknik

Ämneskategorier

Biokemi och molekylärbiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

DOI

10.1093/nar/gkt1397

PubMed

24445803