Ribosome profiling of synchronous, non-arrested yeast cells identifies translational control of lipid biosynthesis enzymes in the cell cycle

The translational efficiency of mRNAs in cells progressing synchronously through the mitotic cell cycle and having to meet their growth requirements for cell division has not been interrogated. Here, we used ribosome profiling of a cell-size series from the time of cell birth, to identify for the first time yeast mRNAs under periodic translational control. Late in the cell cycle, there was coordinate translational activation of mRNAs encoding lipid biosynthesis enzymes. An upstream open reading frame (uORF) mediates the translational control of ACC1, the mRNA encoding the rate-limiting enzyme acetyl-CoA carboxylase. The ACC1 uORF also adjusts Acc1p protein levels in different nutrients. Mutating the ACC1 uORF delayed cell cycle progression, reduced cell size and suppressed the replicative longevity of cells lacking the Sch9p protein kinase, the yeast S6 kinase ortholog. These findings reveal unexpected links between lipogenesis and protein synthesis in mitotic cell divisions