Paper ID: 63
Texas A and M University (USA)
Translational control during cell division determines when cells start a new cell cycle, how fast they complete it, the number of successive divisions, and how cells coordinate proliferation with available nutrients. Translational control in human cells arrested in the cell cycle has been examined previously by ribosome profiling. However, these earlier studies did not query the translational efficiencies of mRNAs in cells progressing synchronously through the mitotic cell cycle, while preserving the coupling of cell division with cell growth. We recently reported comprehensive ribosome profiling of a yeast cell-size series from the time of cell birth, to identify mRNAs under periodic translational control [EMBO J. 2017 36(4):487-502]. We found coordinate translational activation of mRNAs encoding lipogenic enzymes late in the cell cycle including Acc1p, the rate-limiting enzyme acetyl-CoA carboxylase. An upstream open reading frame (uORF) confers the translational control of ACC1 and adjusts Acc1p protein levels in different nutrients. The ACC1 uORF is relevant for cell division because its ablation delays cell cycle progression, reduces cell size, and suppresses the replicative longevity of cells lacking the Sch9p protein kinase regulator of ribosome biogenesis. These findings establish a novel and unexpected relationship between lipogenesis and protein synthesis in mitotic cell divisions. Furthermore, in unpublished work, we found that two conserved proteins that govern duplication of the spindle pole body in the G1 phase, Dsk2p and Mps1p, are under strong, uORF mediated, translational control. These findings link molecularly cell growth and protein synthesis with the machinery for chromosome segregation. Finally, we will present preliminary data from ribosome profiling of ribosomal protein (RP) deletions in the cell cycle, identifying mRNAs under translational control that mediate RP paralog-specific effects on cell division and replicative longevity.