A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation in Drosophila spermatocytes.

During spermatogenesis, cells coordinate differentiation with the meiotic cell cycle to generate functional gametes. We identified a novel gene, which we named off-schedule (ofs), as being essential for this coordinated control. During the meiotic G(2) phase, Drosophila ofs mutant germ cells do not reach their proper size and fail to execute meiosis or significant differentiation. The accumulation of four cell cycle regulators--Cyclin A, Boule, Twine and Roughex--is altered in these mutants, indicating that ofs reveals a novel branch of the pathway controlling meiosis and differentiation. Ofs is homologous to eukaryotic translation initiation factor eIF4G. The level of ofs expression in spermatocytes is much higher than for the known eIF4G ortholog (known as eIF-4G or eIF4G), suggesting that Ofs substitutes for this protein. Consistent with this, assays for association with mRNA cap complexes, as well as RNA-interference and phenotypic-rescue experiments, demonstrate that Ofs has eIF4G activity. Based on these studies, we speculate that spermatocytes monitor G(2) growth as one means to coordinate the initiation of meiotic division and differentiation.

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