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The mitochondrial RNA polymerase contributes critically to promoter specificity in mammalian cells.

Journal article
Authors Martina Gaspari
Maria Falkenberg
Nils-Göran Larsson
Claes M Gustafsson
Published in The EMBO journal
Volume 23
Issue 23
Pages 4606-14
ISSN 0261-4189
Publication year 2004
Published at Institute of Medical Biochemistry
Pages 4606-14
Language en
Links dx.doi.org/10.1038/sj.emboj.7600465
Keywords Animals, Base Sequence, DNA, Mitochondrial, genetics, DNA-Binding Proteins, genetics, DNA-Directed RNA Polymerases, genetics, metabolism, High Mobility Group Proteins, genetics, Humans, Methyltransferases, Mice, Mitochondrial Proteins, genetics, Nuclear Proteins, genetics, Promoter Regions, Genetic, Recombinant Proteins, genetics, Species Specificity, Transcription Factors, genetics, Transcription, Genetic
Subject categories Chemistry

Abstract

Initiation of transcription in mammalian mitochondria depends on three proteins: mitochondrial RNA polymerase (POLRMT), mitochondrial transcription factor A (TFAM) and mitochondrial transcription factor B2 (TFB2M). We show here that the recombinant mouse and human transcription machineries are unable to initiate transcription in vitro from the heterologous light-strand promoter (LSP) of mitochondrial DNA. This species specificity is dependent on the interaction of TFAM and POLRMT with specific distal and proximal promoter elements. A sequence element localized from position -1 to -2 relative to the transcription start site in LSP functionally interacts with POLRMT. The POLRMT/TFB2M heterodimer is unable to interact with promoter elements and initiate even abortive transcription in the absence of TFAM. TFAM is thus an integral part of the mammalian transcription machinery, and we propose that TFAM induces a structural change of the promoter that is required for POLRMT-dependent promoter recognition.

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