Genome-wide screen for cell growth regulators in fission yeast.

Louise Weston,Paul Nurse,Jessica Greenwood

doi:10.1242/jcs.200865

Abstract

ABSTRACTCellular growth control is important for all living organisms, but experimental investigation into this problem is difficult because of the complex range of growth regulatory mechanisms. Here, we have used the fission yeast Schizosaccharomyces pombe to identify potential master regulators of growth. At the restrictive temperature, the S. pombe pat1ts mei4Δ strain enters the meiotic developmental program, but arrests in meiotic G2 phase as mei4+ is essential for meiotic progression. These cells do not grow, even in an abundance of nutrients. To identify regulators of growth that can reverse this growth arrest, we introduced an ORFeome plasmid library into the pat1tsmei4Δ strain. Overexpression of eight genes promoted cell growth; two of these were core RNA polymerase subunits, and one was sck2+, an S6 kinase thought to contribute to TORC1 signalling. Sck2 had the greatest effect on cell growth, and we also show that it significantly increases the cellular transcription rate. These findings indicate, for the first time, that global transcriptional control mediated through S6 kinase signalling is central to cellular growth control.

Highlights

The regulation of cell growth is important for all living organisms
We examined the cell cycle profile of pat1-114 mei4Δ cells that were synchronised by nitrogen starvation prior to meiotic activation
This study has uncovered regulators of cell growth that are independent of nutrient availability

Summary

Introduction

The regulation of cell growth is important for all living organisms. The highly conserved kinase target of rapamycin (TOR) has been shown to play a major role in cell growth through the coordination of numerous cellular processes in response to stress and nutritional changes (Loewith and Hall, 2011). Some downstream effectors have been identified in yeast and mammals, it is still unclear how a positive TOR signal is transduced into cell growth regulation, leading to cell mass accumulation. There is a paucity of assays that measure directly cell growth per se; in particular, a system in which cell growth is switched on in an otherwise non-growing cell has been lacking. Establishing such an assay in a system in which TOR is conserved would illuminate the presently unknown strategies used by cells to activate their growth programme. The rod-shaped fission yeast, Schizosaccharomyces pombe, doubles in mass and length during the cell cycle, generating two daughters of equal size after medial division. Bipolar growth continues until cells enter mitosis, at which point, the cells are held at a constant length until nuclear division

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Conclusion