A systematic genomic screen implicates nucleocytoplasmic transport and membrane growth in nuclear size control.

Kazunori Kume,Frank R Neumann,Andrew W Jones,Ambrosius P Snijders,Helena Cantwell,Paul Nurse,Anita K Hopper

doi:10.1371/journal.pgen.1006767

Kazunori Kume, Frank R Neumann + Show 5 more

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https://doi.org/10.1371/journal.pgen.1006767

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Abstract

How cells control the overall size and growth of membrane-bound organelles is an important unanswered question of cell biology. Fission yeast cells maintain a nuclear size proportional to cellular size, resulting in a constant ratio between nuclear and cellular volumes (N/C ratio). We have conducted a genome-wide visual screen of a fission yeast gene deletion collection for viable mutants altered in their N/C ratio, and have found that defects in both nucleocytoplasmic mRNA transport and lipid synthesis alter the N/C ratio. Perturbing nuclear mRNA export results in accumulation of both mRNA and protein within the nucleus, and leads to an increase in the N/C ratio which is dependent on new membrane synthesis. Disruption of lipid synthesis dysregulates nuclear membrane growth and results in an enlarged N/C ratio. We propose that both properly regulated nucleocytoplasmic transport and nuclear membrane growth are central to the control of nuclear growth and size.

Highlights

Much is known about the molecular mechanisms that underpin membrane trafficking and local membrane growth in eukaryotic cells [1], but how membrane-bound organelles determine their overall growth rate and maintain an appropriate size is not well understood
We screened a near genome-wide fission yeast gene deletion collection for mutants exhibiting aberrant nuclear size, to identify, more systematically, components involved in nuclear size control
Roles for protein complexes previously implicated in nuclear mRNA export and membrane synthesis were identified

Summary

Introduction

Much is known about the molecular mechanisms that underpin membrane trafficking and local membrane growth in eukaryotic cells [1], but how membrane-bound organelles determine their overall growth rate and maintain an appropriate size is not well understood. Budding and fission yeasts exhibit a nuclear size proportional to cell size, resulting in a constant ratio of nuclear and cellular volumes (N/C ratio) [4,5]. In fission yeast the N/C ratio remains constant throughout the cell cycle, and no increase in the ratio is observed during or after S phase; even a 16-fold increase in nuclear DNA content does not affect N/C ratio [5]. These results indicate that, contrary to the generally accepted view, nuclear size is not directly determined by nuclear DNA content. HeLa nuclei increased in volume when injected into the cytoplasm of X. laevis oocytes [8]

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