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Gene Review

RTG1  -  Rtg1p

Saccharomyces cerevisiae S288c

Synonyms: Retrograde regulation protein 1, YOL067C
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High impact information on RTG1

  • Cells containing null alleles of RTG1 and RTG2 are viable and respiratory competent [1].
  • RTG1 encodes a protein of 177 amino acids with similarity to basic helix-loop-helix transcription factors that likely functions at the CIT2 UASr [1].
  • Thus, RTG1 and RTG2 are pivotal genes in controlling interorganelle communication between mitochondria, peroxisomes, and the nucleus [1].
  • Finally, the different effects of lst8 alleles on the activation of either the Rtg1/3p or Gln3p transcription factors reveal that these two pathways constitute distinct, genetically separable outputs of the Tor-Lst8 regulatory complex [2].
  • Here, we report that the Gap1p sorting defect in the lst8-1 mutant results from derepression of Rtg1/3p activity and the subsequent accumulation of high levels of intracellular amino acids, which signal Gap1p sorting to the vacuole [2].

Biological context of RTG1

  • Because rtg1 Delta or rtg3 Delta mutations or the presence of glutamate do not produce the USA+ phenotype, this is a novel function of Rtg2p [3].
  • The R box is a binding site for Rtg1p-Rtg3p, a heterodimeric, basic helix-loop-helix/leucine zipper transcription factor complex [4].
  • Our data show that Rtg1p acts as both a positive and negative regulator of the retrograde response and that Rtg2p acts to transduce mitochondrial signals affecting the phosphorylation state and subcellular localization of Rtg3p [5].
  • In budding yeast, retrograde signaling, also termed the RTG pathway, relies on the heterodimeric, basic helix-loop-helix zipper transcription factors, Rtg1p and Rtg3p, for the activation of target gene expression [6].
  • Transactivation by Rtg1p, a basic helix-loop-helix protein that functions in communication between mitochondria and the nucleus in yeast [7].

Anatomical context of RTG1

  • Two nuclear genes, RTG1 and RTG2, which sense the functional state of yeast mitochondria, have been described recently [8].
  • Although the RTG1 and 2 products proved to be required for the increase in number and volume of peroxisomes upon induction by oleate, the single promoter output of the chosen set of genes remained practically unchanged in a rtg1 mutant strain [9].
  • Transcript profiling of cells harboring null alleles of RTG1, RTG2, or RTG3, genes known to control signaling from mitochondria to the nucleus, suggests that there are multiple pathways of cross-talk between these organelles in yeast [10].

Associations of RTG1 with chemical compounds

  • The TOR-controlled transcription activators GLN3, RTG1, and RTG3 are regulated in response to intracellular levels of glutamine [11].
  • We have examined whether other genes of the glyoxylate cycle exhibit retrograde regulation and the role of RTG1 and RTG2 in their expression [12].
  • Induction of another peroxisomal enzyme, citrate synthase (CIT2) is dependent on the products of two genes called RTG1 and RTG2 (Liao and Butow (1993) Cell 72, 61-71) [9].
  • Mechanism of metabolic control. Target of rapamycin signaling links nitrogen quality to the activity of the Rtg1 and Rtg3 transcription factors [13].
  • Expression of these genes in media containing urea or ammonia as a sole nitrogen source requires the heterodimeric bZip transcription factors Rtg1 and Rtg3 and correlates with a redistribution of the Rtg1p/Rtg3 complex from a predominantly cytoplasmic to a predominantly nuclear location [13].

Physical interactions of RTG1

  • Rtg3p binds together with Rtg1p to two identical sites oriented as inverted repeats 28 bp apart in a regulatory upstream activation sequence element (UASr) in the CIT2 promoter [14].
  • Rtg3p and Rtg1p are basic helix-loop-helix/leucine zipper protein transcription factors in yeast that interact and bind to sites in an upstream activation sequence element in the 5'-flanking region of CIT2, a gene encoding a peroxisomal isoform of citrate synthase [15].

Regulatory relationships of RTG1

  • Rtg2p regulates transcription of glutamate-repressible genes by facilitation of the nuclear entry of the Rtg1 and Rtg3 proteins [3].
  • Rtg1p is a basic helix-loop-helix transcription factor in the yeast Saccharomyces cerevisiae that is required for basal and regulated expression of CIT2, the gene encoding a peroxisomal isoform of citrate synthase [7].

Other interactions of RTG1

  • Previous studies identified a basic helix-loop-helix-leucine zipper (bHLH/Zip) transcription factor encoded by the RTG1 gene that is required for both basal expression of the CIT2 gene and its increased expression in respiratory-deficient cells [14].
  • Other Gal4p fusions to deletions or mutations of Rtg1p indicate that the helix-loop-helix domain is essential for transactivation [7].

Analytical, diagnostic and therapeutic context of RTG1


  1. RTG1 and RTG2: two yeast genes required for a novel path of communication from mitochondria to the nucleus. Liao, X., Butow, R.A. Cell (1993) [Pubmed]
  2. LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway. Chen, E.J., Kaiser, C.A. J. Cell Biol. (2003) [Pubmed]
  3. A novel Rtg2p activity regulates nitrogen catabolism in yeast. Pierce, M.M., Maddelein, M.L., Roberts, B.T., Wickner, R.B. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. A transcriptional switch in the expression of yeast tricarboxylic acid cycle genes in response to a reduction or loss of respiratory function. Liu, Z., Butow, R.A. Mol. Cell. Biol. (1999) [Pubmed]
  5. Mitochondria-to-nuclear signaling is regulated by the subcellular localization of the transcription factors Rtg1p and Rtg3p. Sekito, T., Thornton, J., Butow, R.A. Mol. Biol. Cell (2000) [Pubmed]
  6. Interaction between Rtg2p and Mks1p in the regulation of the RTG pathway of Saccharomyces cerevisiae. Ferreira Júnior, J.R., Spírek, M., Liu, Z., Butow, R.A. Gene (2005) [Pubmed]
  7. Transactivation by Rtg1p, a basic helix-loop-helix protein that functions in communication between mitochondria and the nucleus in yeast. Rothermel, B.A., Shyjan, A.W., Etheredge, J.L., Butow, R.A. J. Biol. Chem. (1995) [Pubmed]
  8. Enzymatic and metabolic studies on retrograde regulation mutants of yeast. Small, W.C., Brodeur, R.D., Sandor, A., Fedorova, N., Li, G., Butow, R.A., Srere, P.A. Biochemistry (1995) [Pubmed]
  9. Expression of genes encoding peroxisomal proteins in Saccharomyces cerevisiae is regulated by different circuits of transcriptional control. Kos, W., Kal, A.J., van Wilpe, S., Tabak, H.F. Biochim. Biophys. Acta (1995) [Pubmed]
  10. Genome-wide responses to mitochondrial dysfunction. Epstein, C.B., Waddle, J.A., Hale, W., Davé, V., Thornton, J., Macatee, T.L., Garner, H.R., Butow, R.A. Mol. Biol. Cell (2001) [Pubmed]
  11. The TOR-controlled transcription activators GLN3, RTG1, and RTG3 are regulated in response to intracellular levels of glutamine. Crespo, J.L., Powers, T., Fowler, B., Hall, M.N. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  12. RTG genes in yeast that function in communication between mitochondria and the nucleus are also required for expression of genes encoding peroxisomal proteins. Chelstowska, A., Butow, R.A. J. Biol. Chem. (1995) [Pubmed]
  13. Mechanism of metabolic control. Target of rapamycin signaling links nitrogen quality to the activity of the Rtg1 and Rtg3 transcription factors. Komeili, A., Wedaman, K.P., O'Shea, E.K., Powers, T. J. Cell Biol. (2000) [Pubmed]
  14. A basic helix-loop-helix-leucine zipper transcription complex in yeast functions in a signaling pathway from mitochondria to the nucleus. Jia, Y., Rothermel, B., Thornton, J., Butow, R.A. Mol. Cell. Biol. (1997) [Pubmed]
  15. Rtg3p, a basic helix-loop-helix/leucine zipper protein that functions in mitochondrial-induced changes in gene expression, contains independent activation domains. Rothermel, B.A., Thornton, J.L., Butow, R.A. J. Biol. Chem. (1997) [Pubmed]
  16. The retrograde response links metabolism with stress responses, chromatin-dependent gene activation, and genome stability in yeast aging. Jazwinski, S.M. Gene (2005) [Pubmed]
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