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Gene Review

MTF1  -  Mtf1p

Saccharomyces cerevisiae S288c

Synonyms: Mitochondrial transcription factor 1, Mitochondrial transcription factor mtTFB, Mitochondrial-specificity factor, RF1023, YM9959.10, ...
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Disease relevance of MTF1

  • After expression in Escherichia coli or purification from yeast mitochondria, two proteins were tested; they were ABF2 (a structural homologue of the human mitochondrial transcriptional activator mtTF1) and MTF1 (the gene product of a yeast locus known to exhibit a mitochondrial transcription phenotype) [1].
  • The yeast mitochondrial RNA polymerase is composed of two nuclear encoded subunits, a catalytic core (Rpo41p), which resembles the enzymes from bacteriophage T7 and T3, and a specificity factor required for promoter recognition (Mtf1p), which is similar to members of the eubacterial sigma factor family [2].

High impact information on MTF1

  • We have used two-hybrid and fusion protein constructs to analyze the requirements for interaction between the single subunit core polymerase (Rpo41p), and the sigma-like promoter specificity factor (Mtf1p) [3].
  • We found that 9 of 15 nonfunctional (petite) point mutations in Mtf1p isolated in a plasmid shuffle strategy had lost the ability to interact [3].
  • Transcriptional induction of metallothionein genes is mediated by the metal-responsive transcription factor 1 (MTF-1), an essential zinc finger protein that binds to specific DNA motifs termed metal-response elements [4].
  • In cell-free DNA binding reactions with nuclear extracts, MTF-1 requires elevated zinc concentrations for efficient DNA binding but paradoxically is inactivated by other in vivo inducers such as cadmium, copper, and hydrogen peroxide [4].
  • Using in organello import experiments, we found that p43 is targeted to the organelle by an unusual process similar to that previously reported for MTF1, a yeast mitochondrial transcription factor [5].

Biological context of MTF1

  • A point mutation in the core subunit gene of yeast mitochondrial RNA polymerase is suppressed by a high level of specificity factor MTF1 [6].
  • Comparison of the 5' upstream regions of MTF2 and a previously characterized mitochondrial transcription factor (MTF1) revealed common sequence motifs which may be important for coordinated regulation of gene expression [7].
  • Unlike most of the mitochondrial precursor proteins studied so far, import of MTF1 does not appear to require a receptor on the outer membrane, membrane potential across the inner membrane, or ATP hydrolysis [8].
  • The MTF1 gene was physically mapped to chromosome XIII [9].
  • As the specificity factor is the key component for initiation of transcription at the mitochondrial promoter we wanted to study in more detail gene expression, regulation, and the function of the promoter of the nuclear MTF1 gene [10].

Anatomical context of MTF1

  • These Mtf1p derivatives were generated either in the RRL (rabbit reticulocyte lysate) or in the WGE (wheat germ extract) translation system [11].
  • By contrast, activation domains from cellular eukaryotic transcription factors (TFE3, ITF2, MTF-1) are differentially active in oocytes and early embryos [12].

Other interactions of MTF1

  • These genes do not appear to regulate mitochondrial transcript levels via regulation of the nuclear genes RPO41 and MTF1, which encode the subunits of the mitochondrial RNA polymerase [13].
  • The results show that MTF1 specifies correct transcriptional initiation while ABF2 does not [1].
  • Over-expression of Azf1p in the yeast cell does not influence the expression level of the mitochondrial transcription factor Mtf1p, indicating that the influence of Azf1p on the suppression of the special mitochondrial RNA polymerase mutant is an indirect one [14].

Analytical, diagnostic and therapeutic context of MTF1


  1. Assignment of a yeast protein necessary for mitochondrial transcription initiation. Xu, B., Clayton, D.A. Nucleic Acids Res. (1992) [Pubmed]
  2. Release of the yeast mitochondrial RNA polymerase specificity factor from transcription complexes. Mangus, D.A., Jang, S.H., Jaehning, J.A. J. Biol. Chem. (1994) [Pubmed]
  3. Identification of three regions essential for interaction between a sigma-like factor and core RNA polymerase. Cliften, P.F., Park, J.Y., Davis, B.P., Jang, S.H., Jaehning, J.A. Genes Dev. (1997) [Pubmed]
  4. Activity of metal-responsive transcription factor 1 by toxic heavy metals and H2O2 in vitro is modulated by metallothionein. Zhang, B., Georgiev, O., Hagmann, M., Günes, C., Cramer, M., Faller, P., Vasák, M., Schaffner, W. Mol. Cell. Biol. (2003) [Pubmed]
  5. A variant form of the nuclear triiodothyronine receptor c-ErbAalpha1 plays a direct role in regulation of mitochondrial RNA synthesis. Casas, F., Rochard, P., Rodier, A., Cassar-Malek, I., Marchal-Victorion, S., Wiesner, R.J., Cabello, G., Wrutniak, C. Mol. Cell. Biol. (1999) [Pubmed]
  6. A point mutation in the core subunit gene of yeast mitochondrial RNA polymerase is suppressed by a high level of specificity factor MTF1. Riemen, G., Michaelis, G. Mol. Gen. Genet. (1993) [Pubmed]
  7. Molecular analysis of the mitochondrial transcription factor mtf2 of Saccharomyces cerevisiae. Lisowsky, T. Mol. Gen. Genet. (1990) [Pubmed]
  8. Import of transcription factor MTF1 into the yeast mitochondria takes place through an unusual pathway. Sanyal, A., Getz, G.S. J. Biol. Chem. (1995) [Pubmed]
  9. MTF1, encoding the yeast mitochondrial RNA polymerase specificity factor, is located on chromosome XIII. Ulery, T.L., Jaehning, J.A. Yeast (1994) [Pubmed]
  10. Expression studies and promoter analysis of the nuclear gene for mitochondrial transcription factor 1 (MTF1) in yeast. Jan, P.S., Stein, T., Hehl, S., Lisowsky, T. Curr. Genet. (1999) [Pubmed]
  11. Requirement of different mitochondrial targeting sequences of the yeast mitochondrial transcription factor Mtf1p when synthesized in alternative translation systems. Biswas, T.K., Getz, G.S. Biochem. J. (2004) [Pubmed]
  12. Different potential of cellular and viral activators of transcription revealed in oocytes and early embryos of Xenopus laevis. Xu, L., Rungger, D., Georgiev, O., Seipel, K., Schaffner, W. Biol. Chem. Hoppe-Seyler (1994) [Pubmed]
  13. Glucose repression of yeast mitochondrial transcription: kinetics of derepression and role of nuclear genes. Ulery, T.L., Jang, S.H., Jaehning, J.A. Mol. Cell. Biol. (1994) [Pubmed]
  14. Azf1p is a nuclear-localized zinc-finger protein that is preferentially expressed under non-fermentative growth conditions in Saccharomyces cerevisiae. Stein, T., Kricke, J., Becher, D., Lisowsky, T. Curr. Genet. (1998) [Pubmed]
  15. A mutation in the yeast mitochondrial core RNA polymerase, Rpo41, confers defects in both specificity factor interaction and promoter utilization. Matsunaga, M., Jaehning, J.A. J. Biol. Chem. (2004) [Pubmed]
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