Translational control of MPS1 links protein synthesis with the initiation of cell division and spindle pole body duplication in yeast

Abstract

ABSTRACTProtein synthesis underpins cell growth and controls when cells commit to a new round of cell division at a point in late G1 of the cell cycle called Start. Passage through Start also coincides with the duplication of the microtubule-organizing centers, the yeast spindle pole bodies, which will form the two poles of the mitotic spindle that segregates the chromosomes in mitosis. The conserved Mps1p kinase governs the duplication of the spindle pole body in Saccharomyces cerevisiae. Here, we show that the MPS1 transcript has a short upstream open reading frame that represses the synthesis of Mps1p. Mutating the MPS1 uORF makes the cells smaller, accelerates the appearance of Mps1p in late G1, and promotes completion of Start. The accelerated Start of MPS1 uORF mutants depends on the G1 cyclin Cln3p. Monitoring the spindle pole body in the cell cycle using structured illumination microscopy revealed that mutating the MPS1 uORF enabled cells to duplicate their spindle pole body earlier, at a smaller cell size. For the first time, these results identify growth inputs in mechanisms that control duplication of the microtubule-organizing center and implicate these processes in general mechanisms that couple growth with division.