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The amino terminal extension of mammalian mitochondrial RNA polymerase ensures promoter specific transcription initiation.


ABSTRACT: 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 single-subunit 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 non-specific 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.

SUBMITTER: Posse V 

PROVIDER: S-EPMC3973307 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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The amino terminal extension of mammalian mitochondrial RNA polymerase ensures promoter specific transcription initiation.

Posse Viktor V   Hoberg Emily E   Dierckx Anke A   Shahzad Saba S   Koolmeister Camilla C   Larsson Nils-Göran NG   Wilhelmsson L Marcus LM   Hällberg B Martin BM   Gustafsson Claes M CM  

Nucleic acids research 20140120 6


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 single-subunit 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 initiat  ...[more]

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