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

Author:

Blank Heidi M1,Alonso Annabel2,Fabritius Amy S2,Valk Ervin3,Loog Mart3,Winey Mark2,Polymenis Michael1ORCID

Affiliation:

1. Department of Biochemistry and Biophysics, Texas A&M University , 2128 TAMU, College Station, TX 77843 , USA

2. Department of Molecular and Cellular Biology, University of California, Davis , Davis, CA 95616 , USA

3. Institute of Technology, University of Tartu , Tartu 50411 , Estonia

Abstract

Abstract Protein 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 2 poles of the mitotic spindle that segregates the chromosomes in mitosis. The conserved Mps1p kinase governs the duplication of the spindle pole body (SPB) in Saccharomyces cerevisiae. Here, we show that the MPS1 transcript has a short upstream open reading frame (uORF) 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. Monitoring the SPB in the cell cycle using structured illumination microscopy revealed that mutating the MPS1 uORF enabled cells to duplicate their SPB earlier at a smaller cell size. The accelerated Start of MPS1 uORF mutants depends on the G1 cyclin Cln3p and the transcriptional repressor Whi5p but not on the Cln1,2p G1 cyclins. These results identify growth inputs in mechanisms that control duplication of the microtubule-organizing center and implicate these processes in the coupling of cell growth with division.

Funder

NIH

Oncogenic Signals and Chromosome Biology Training

Publisher

Oxford University Press (OUP)

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