Fission Yeast Int6 Is Not Essential for Global Translation Initiation, but Deletion ofint6+Causes Hypersensitivity to Caffeine and Affects Spore Formation

Abstract

Mammalian INT6 protein has been considered to be a subunit of the eukaryotic translation initiation factor, eIF3. The Int6 locus is also known as a common integration site of mousemammary tumor virus (MMTV). However, the function of Int6 in translation initiation and the mechanism of Int6-mediated tumor induction are yet to be explored. In this study, the fission yeast, Schizosaccharomyces pombe, int6+, which is 43% identical to the mammalian counterpart, was deleted. Despite the evidence that the majority of Int6 protein was associated with 40S particles in this organism, strains lackingint6+(Δ int6) were viable and showed only moderate inhibition in the rate of in vivo global protein synthesis. Polysome profile analysis showed no apparent defects in translation initiation. Δ int6 exhibited a hypersensitivity to caffeine, which could be suppressed by the addition of sorbitol to the growth medium. This and other phenotypes would imply that int6+is required for the integrity of cell membrane. In meiosis, Δ int6produced incomplete tetrads frequently. High dosage expression of a truncated mutant of int6+conferred a hypersensitivity to caffeine, but did not cause the defect in meiosis. A possible link between the function ofint6+and theΔ int6-phenotypes is discussed.