The nucleoporin ELYS regulates nuclear size by controlling NPC number and nuclear import capacity

Abstract

How intracellular organelles acquire their characteristic sizes is a fundamental question in cell biology. Given stereotypical changes in nuclear size in cancer, it is important to understand the mechanisms that control nuclear size in human cells. Using a high‐throughput imaging RNAi screen, we identify and mechanistically characterize ELYS, a nucleoporin required for post‐mitotic nuclear pore complex (NPC) assembly, as a determinant of nuclear size in mammalian cells. ELYS knockdown results in small nuclei, reduced nuclear lamin B2 localization, lower NPC density, and decreased nuclear import. Increasing nuclear import by importin α overexpression rescues nuclear size and lamin B2 import, while inhibiting importin α/β‐mediated nuclear import decreases nuclear size. Conversely, ELYS overexpression increases nuclear size, enriches nuclear lamin B2 at the nuclear periphery, and elevates NPC density and nuclear import. Consistent with these observations, knockdown or inhibition of exportin 1 increases nuclear size. Thus, we identify ELYS as a novel positive effector of mammalian nuclear size and propose that nuclear size is sensitive to NPC density and nuclear import capacity.

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A homeostatic mechanism rapidly corrects aberrant nucleocytoplasmic ratios maintaining nuclear size in fission yeast

“…In the budding and fission yeasts, it has been proposed that nuclear volume ( V nuc ) scales with cellular volume ( V cell ) (Jorgensen et al, 2007; Neumann and Nurse, 2007) and in the case of fission yeast, a nuclear to cellular volume (N/C) ratio of 8% is maintained over a 35-fold range of cell volumes. Although 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, 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.…”