Disease relevance of TIF6

• The Saccharomyces cerevisiae gene that encodes the 245-amino-acid eIF6 (calculated Mr 25,550), designated TIF6, has been cloned and expressed in Escherichia coli [2].

High impact information on TIF6

• Here, we identify the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes [3].
• Using genome-wide synthetic genetic array mapping, we identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1Delta cells [3].
• We further demonstrate that ARB1 shuttles from nucleus to cytoplasm, cosediments with 40S, 60S, and 80S/90S ribosomal species, and is physically associated in vivo with TIF6, LSG1, and other proteins implicated previously in different aspects of 60S or 40S biogenesis [4].
• When both Ser-174 and Ser-175 were mutated to alanine, phosphorylation of Tif6p was completely abolished [5].
• The Saccharomyces cerevisiae TIF6 gene encoding translation initiation factor 6 is required for 60S ribosomal subunit biogenesis [6].

Biological context of TIF6

• In the case of a 22-residue C-terminal deletion this can be suppressed by intragenic mutations in the RIA1 gene or dominant extragenic mutations in TIF6, which is thought to be involved in the biogenesis of the 60S subunit of the ribosome [7].
• The dominant TIF6 alleles can also suppress the phenotype associated with a complete deletion of the RIA1 gene [7].
• Depletion of eIF6 from yeast cells resulted in a decrease in the rate of protein synthesis, accumulation of half-mer polyribosomes, reduced levels of 60S ribosomal subunits resulting in the stoichiometric imbalance in the 40S/60S subunit ratio, and ultimately cessation of cell growth [2].
• These results suggest that phosphorylatable Ser-174 and Ser-175 play a critical role in the nuclear export of Tif6p [5].
• In Saccharomyces cerevisiae, eIF6 is encoded by a single-copy essential gene [6].

Anatomical context of TIF6

• At the end of gastrulation, the p27BBP/eIF6 riboprobe localizes in the neural plate and in the paraxial mesoderm [8].
• In embryos exposed to teratogens, the localization of p27BBP/eIF6 riboprobe varies according to the change of head size caused by the treatment. p27BBP/eIF6 expression is particularly evident in differentiating olfactory pits, the lens, otic vesicles, and in branchial arches [8].

Other interactions of TIF6

• To understand the function of eIF6 in yeast cells, we constructed a conditional mutant haploid yeast strain in which a functional but a rapidly degradable form of eIF6 fusion protein was synthesized from a repressible GAL10 promoter [6].
• Finally, we confirm that Tif6p accompanies 27S pre-rRNA maturation to 25S rRNA and we suggest that Sen34p endonuclease in Tif6p complex may affect also rRNA maturation [9].
• Tif6p is phosphorylated both in vitro and in vivo by Hrr25p, an isoform of yeast casein kinase I . Tryptic phosphopeptide mapping of in vitro phosphorylated Tif6p by Hrr25p and ³²P-labeled Tif6p isolated from yeast cells followed by mass spectrometric analysis revealed that phosphorylation occurred on a single tryptic peptide at Ser-174 [1].

Analytical, diagnostic and therapeutic context of TIF6

• Cell fractionation as well as indirect immunofluorescence studies showed that c-Myc or hemagglutinin epitope-tagged eIF6 was distributed throughout the cytoplasm and the nuclei of yeast cells [6].

References