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About the Authors:
Kazunori Kume
* E-mail: [email protected]
Affiliations Hiroshima Research Center for Healthy Aging, Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan, Cell Cycle Laboratory, The Francis Crick Institute, London, United Kingdom
Helena Cantwell
Affiliation: Cell Cycle Laboratory, The Francis Crick Institute, London, United Kingdom
ORCID http://orcid.org/0000-0002-7714-995X
Frank R. Neumann
Affiliation: Laboratory of Yeast Genetics and Cell Biology, Rockefeller University, New York, New York, United States of America
Andrew W. Jones
Affiliations Cell Cycle Laboratory, The Francis Crick Institute, London, United Kingdom, Protein Analysis and Proteomics Platform, The Francis Crick Institute, London, United Kingdom
Ambrosius P. Snijders
Affiliation: Protein Analysis and Proteomics Platform, The Francis Crick Institute, London, United Kingdom
ORCID http://orcid.org/0000-0002-5416-8592
Paul Nurse
Affiliations Cell Cycle Laboratory, The Francis Crick Institute, London, United Kingdom, Laboratory of Yeast Genetics and Cell Biology, Rockefeller University, New York, New York, United States of AmericaAbstract
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.
Author summary
Membrane-bound organelles are maintained at a size proportional to cell size during cell growth and division. How this is achieved is a little-understood area of cell biology. The nucleus is generally present in single copy within a cell and provides a useful model to study overall membrane-bound organelle growth and organelle size homeostasis. Previous mechanistic studies of nuclear size control have been limited to cell-free nuclear assembly systems. Here, we screened a near...