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Gene Review

TIF3  -  Tif3p

Saccharomyces cerevisiae S288c

Synonyms: Eukaryotic translation initiation factor 4B, P9325.6, RBL3, STM1, TIF42, ...
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Disease relevance of TIF3

  • Functionally, targeted disruption of the STM1 gene results in rapamycin hypersensitivity and a defect in recovery following nitrogen starvation and replenishment [1].

High impact information on TIF3

  • Tif3-His6p stimulates translation and mRNA binding to ribosomes in a Tif3-dependent in vitro system [2].
  • We have added six histidine residues to the C-terminus of Tif3 protein (Tif3-His6p) and purified the tagged protein by affinity chromatography [2].
  • The TIF3 gene is not essential for growth; however, its disruption results in a slow growth and cold-sensitive phenotype [3].
  • The Stm1 protein has potential RNP1 and RNP2 motifs characteristic for RNA-binding proteins [4].
  • This indicates that Tif3 protein is an RNA helicase or contributes to RNA helicase activity in vivo [3].

Biological context of TIF3


Anatomical context of TIF3

  • In its association with ribosomes, Stm1p interacts in an equimolar complex with both ribosomal subunits and is not associated with mRNA [1].
  • Using a variety of biochemical methods, we found that the vast majority of cellular Stm1p is associated with free cytosolic 80S ribosomes and polysomes [1].

Associations of TIF3 with chemical compounds

  • Plant eIF4B contains three RNA binding domains, one more than reported for mammalian or yeast eIF4B, and each domain exhibits a preference for purine-rich RNA [8].
  • In addition to a conserved RNA recognition motif and a C-terminal RNA binding domain, wheat eIF4B contains a novel N-terminal RNA binding domain that requires a short, lysine-rich containing sequence [8].
  • Cells lacking Stm1 display deficiency in the apoptosis-like cell death process induced by treatment with low concentrations of H(2)O(2) [6].
  • This association was verified by rate zonal separation through sucrose gradients, which showed that Stm1p binds exclusively to mature 80 S ribosomes and polysomes [7].
  • STM1, a gene which encodes a guanine quadruplex binding protein, interacts with CDC13 in Saccharomyces cerevisiae [9].

Regulatory relationships of TIF3

  • In wheat germ, the combination of eIF-4A and eIF-4F resulted in RNA unwinding in a reaction that was stimulated by eIF-4B [10].

Other interactions of TIF3

  • Ribosome binding to eukaryotic mRNAs requires the concerted action of three eukaryotic initiation factors: eIF-4A, eIF-4B and eIF-4F as well as the hydrolysis of ATP [10].

Analytical, diagnostic and therapeutic context of TIF3


  1. Stm1p, a Ribosome-associated Protein, is Important for Protein Synthesis in Saccharomyces cerevisiae under Nutritional Stress Conditions. Van Dyke, N., Baby, J., Van Dyke, M.W. J. Mol. Biol. (2006) [Pubmed]
  2. The Saccharomyces cerevisiae translation initiation factor Tif3 and its mammalian homologue, eIF-4B, have RNA annealing activity. Altmann, M., Wittmer, B., Méthot, N., Sonenberg, N., Trachsel, H. EMBO J. (1995) [Pubmed]
  3. A Saccharomyces cerevisiae homologue of mammalian translation initiation factor 4B contributes to RNA helicase activity. Altmann, M., Müller, P.P., Wittmer, B., Ruchti, F., Lanker, S., Trachsel, H. EMBO J. (1993) [Pubmed]
  4. A new yeast translation initiation factor suppresses a mutation in the eIF-4A RNA helicase. Coppolecchia, R., Buser, P., Stotz, A., Linder, P. EMBO J. (1993) [Pubmed]
  5. Translation initiation factor 4A from Saccharomyces cerevisiae: analysis of residues conserved in the D-E-A-D family of RNA helicases. Schmid, S.R., Linder, P. Mol. Cell. Biol. (1991) [Pubmed]
  6. The proteasomal substrate Stm1 participates in apoptosis-like cell death in yeast. Ligr, M., Velten, I., Fröhlich, E., Madeo, F., Ledig, M., Fröhlich, K.U., Wolf, D.H., Hilt, W. Mol. Biol. Cell (2001) [Pubmed]
  7. Stm1p, a G4 quadruplex and purine motif triplex nucleic acid-binding protein, interacts with ribosomes and subtelomeric Y' DNA in Saccharomyces cerevisiae. Van Dyke, M.W., Nelson, L.D., Weilbaecher, R.G., Mehta, D.V. J. Biol. Chem. (2004) [Pubmed]
  8. Wheat eukaryotic initiation factor 4B organizes assembly of RNA and eIFiso4G, eIF4A, and poly(A)-binding protein. Cheng, S., Gallie, D.R. J. Biol. Chem. (2006) [Pubmed]
  9. STM1, a gene which encodes a guanine quadruplex binding protein, interacts with CDC13 in Saccharomyces cerevisiae. Hayashi, N., Murakami, S. Mol. Genet. Genomics (2002) [Pubmed]
  10. Translation initiation factors that function as RNA helicases from mammals, plants and yeast. Jaramillo, M., Browning, K., Dever, T.E., Blum, S., Trachsel, H., Merrick, W.C., Ravel, J.M., Sonenberg, N. Biochim. Biophys. Acta (1990) [Pubmed]
  11. A 110-kilodalton subunit of translation initiation factor eIF3 and an associated 135-kilodalton protein are encoded by the Saccharomyces cerevisiae TIF32 and TIF31 genes. Vornlocher, H.P., Hanachi, P., Ribeiro, S., Hershey, J.W. J. Biol. Chem. (1999) [Pubmed]
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