Fission yeast homolog of murine int-6 protein, encoded by mouse mammary tumor virus integration site, is associated with the conserved core subunits of eukaryotic translation initiation factor 3

The murine int-6 locus, identified as a frequent integration site of mouse mammary tumor viruses, encodes the 48-kDa eIF3e subunit of translation init iation factor eIF3, Previous studies indicated that the catalytically activ e core of budding yeast eIF3 consists of five subunits, all conserved in eu karyotes, but does not contain a protein closely related to eIF3e/Int-6, Wh ereas the budding yeast genome does not encode a protein closely related to murine Int-6, fission yeast does encode an Int-6 ortholog, designated here Int6, We found that fission yeast Int6/eIF3e is a cytoplasmic protein asso ciated with 40 S ribosomes, FLAG epitope-tagged Tif35,a putative core eIF3g subunit, copurified with Int6 and all five orthologs of core eIF3 subunits , An int6 deletion (int6 Delta) mutant was viable but grew slowly in minima l medium. This slow growth phenotype was accompanied by a reduction in the amount of polyribosomes engaged in translation and was complemented by expr ession of human Int-6 protein. These findings support the idea that human a nd Schizosaccharomyces pombe Int-6 homologs are involved in translation. In terestingly, haploid int6 Delta cells showed unequal nuclear partitioning, possibly because of a defect in tubulin function, and diploid int6 Delta ce lls formed abnormal spores. We propose that Int6 is not an essential subuni t of eIF3 but might be involved in regulating the activity of eIF3 for tran slation of specific mRNAs in S. pombe.