Abstract

ABSTRACTNuclear size scales with cell size across a wide range of cell types. The mechanism by which this scaling is maintained in growing cells remains unclear. Here, we investigate the mechanism of nuclear size homeostasis in the simple eukaryote fission yeast, by monitoring the recovery of aberrant nuclear volume to cell volume (N/C) ratios following perturbation. We demonstrate that both high and low N/C ratios correct rapidly, maintaining nuclear size homeostasis. We assess the kinetics of nuclear and cellular growth and of N/C ratio correction, and demonstrate that nuclear and cellular growth rates are not directly coupled. We propose that the mechanism underlying nuclear size homeostasis involves multiple limiting factors implicated in processes including nucleocytoplasmic transport, lipid biogenesis and RNA processing. We speculate that these link cellular size increases to changes in nuclear contents, which in turn lead to changes in nuclear membrane surface area. Our study reveals that there is rapid nuclear size homeostasis in cells, informing understanding of nuclear size control and size homeostasis of other membrane-bound organelles.

Highlights

  • Membrane bound organelles increase in size as cells grow

  • We investigate the mechanism of nuclear size homeostasis in the simple eukaryote fission yeast, by monitoring the recovery of aberrant nuclear volume to cell volume (N/C) ratios following perturbation

  • We demonstrate that both high and low nuclear to cellular volume (N/C) ratios correct rapidly, maintaining nuclear size homeostasis

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Summary

Introduction

Membrane bound organelles increase in size as cells grow. the mechanisms ensuring organellar size and membrane growth are coordinated with cellular growth are not well understood. Though recent studies have identified some molecular players and biological processes with roles in nuclear size control (Brownlee and Heald, 2019; Cantwell and Nurse, 2019; Jevtić et al, 2019; Kume et al, 2019; Kume et al, 2017), it is not known how these are integrated in a global mechanism to maintain nuclear scaling in individual cells as they grow and divide. Investigation of this mechanism requires understanding of the kinetics of this process, in particular of how individual cells with aberrant N/C ratios correct towards the population mean and what this implies for the nuclear size control mechanisms employed by cells

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