A human mitochondrial transcription factor is related to RNA adenine methyltransferases and binds S-adenosylmethionine

Mol Cell Biol. 2002 Feb;22(4):1116-25. doi: 10.1128/MCB.22.4.1116-1125.2002.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Green Fluorescent Proteins
  • HeLa Cells
  • Humans
  • Luminescent Proteins / metabolism
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Microscopy, Fluorescence
  • Mitochondria / chemistry
  • Mitochondria / physiology*
  • Mitochondrial Proteins*
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Recombinant Fusion Proteins / metabolism
  • S-Adenosylmethionine / genetics
  • S-Adenosylmethionine / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Alignment
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Luminescent Proteins
  • Mitochondrial Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • TFAM protein, human
  • TFB1M protein, human
  • Transcription Factors
  • mitochondrial transcription factor A
  • Green Fluorescent Proteins
  • S-Adenosylmethionine
  • Methyltransferases