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

• Likewise, Stm1p has been identified as a protein associated with supramolecular structures, including ribosomes and nuclear telomere cap complexes [1].
• The deduced amino acid sequence shows 26% identity with the sequence of mammalian translation initiation factor eIF-4B [3].
• This activity is dependent on ATP hydrolysis and the presence of another translation initiation factor, eIF-4B [5].
• Conversely, Stm1 accumulation induces cell death [6].
• Chromatin immunoprecipitation experiments found that Stm1p preferentially binds telomere-proximal Y' element DNA sequences [7].

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

• Sequence analysis revealed interesting features of the putative Stm1 protein [4].
• Conventional immunoprecipitation found that Stm1p is associated with ribosomal proteins and rRNA [7].
• Indirect immunofluorescence microscopy indicated that Stm1p is primarily a cytoplasmic protein, although a small percentage is also present in the nucleus [7].
• Far Western blotting and two-hybrid analyses detect a direct interaction of p110 with p90, p135 with p33, and p33 with eIF4B [11].

References