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Molecular and Cellular Biology, February 2002, p. 1116-1125, Vol. 22, No. 4
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.4.1116-1125.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

A Human Mitochondrial Transcription Factor Is Related to RNA Adenine Methyltransferases and Binds S-Adenosylmethionine

Vicki McCulloch, Bonnie L. Seidel-Rogol, and Gerald S. Shadel*

Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, Atlanta, Georgia 30322

Received 8 August 2001/ Returned for modification 17 September 2001/ Accepted 16 November 2001

A critical step toward understanding mitochondrial genetics and its impact on human disease is to identify and characterize the full complement of nucleus-encoded factors required for mitochondrial gene expression and mitochondrial DNA (mtDNA) replication. Two factors required for transcription initiation from a human mitochondrial promoter are h-mtRNA polymerase and the DNA binding transcription factor, h-mtTFA. However, based on studies in model systems, the existence of a second human mitochondrial transcription factor has been postulated. Here we report the isolation of a cDNA encoding h-mtTFB, the human homolog of Saccharomyces cerevisiae mitochondrial transcription factor B (sc-mtTFB) and the first metazoan member of this class of transcription factors to which a gene has been assigned. Recombinant h-mtTFB is capable of binding mtDNA in a non-sequence-specific fashion and activates transcription from the human mitochondrial light-strand promoter in the presence of h-mtTFA in vitro. Remarkably, h-mtTFB and its fungal homologs are related in primary sequence to a superfamily of N6 adenine RNA methyltransferases. This observation, coupled with the ability of recombinant h-mtTFB to bind S-adenosylmethionine in vitro, suggests that a structural, and perhaps functional, relationship exists between this class of transcription factors and this family of RNA modification enzymes and that h-mtTFB may perform dual functions during mitochondrial gene expression.

* Corresponding author. Mailing address: Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, Atlanta, GA 30322. Phone: (404) 727-3798. Fax: (404) 727-3954. E-mail: gshadel{at}emory.edu.

Molecular and Cellular Biology, February 2002, p. 1116-1125, Vol. 22, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.4.1116-1125.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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