Nucleolar size regulates nuclear envelope shape in Saccharomyces cerevisiae

Abstract

Nuclear shape and size are cell type-specific. Change in nuclear shape is seen during cell division, development, and pathology. The nucleus of S. cerevisiae is spherical in interphase and becomes dumb-bell shaped during mitotic division to facilitate the transfer of one nucleus to the daughter cell. As yeast cells undergo closed mitosis, the nuclear envelope remains intact throughout the cell cycle. The pathways that regulate nuclear shape are not well characterized. The nucleus is organized into various sub-compartments, with the nucleolus being the most prominent. We have initiated a candidate-based genetic screen for nuclear shape abnormalities in S. cerevisiae to ask if the nucleolus influences the nuclear shape. We find that increasing nucleolar volume triggers a non-isometric nuclear envelope expansion resulting in an abnormal nuclear envelope shape. We further show that the tethering of rDNA to the nuclear envelope is required for the appearance of these extensions.

Regulation of diverse nuclear shapes: pathways working independently, together

“…Attachment of chromatin to lamins and INM proteins provides another layer of regulation for genome organization and the basis for mechanical changes in the NE. In budding yeast, the association of chromatin with NE proteins like Esc1, Mps3, Heh1 and Heh2, means that a change in chromosome structure could potentially affect the NE by altering the tethering [22,[40][41][42]. The role of lamins and other NE proteins in nuclear shape regulation will be discussed in the following sections.…”

“…In the tunicate Ciona , two lamin variants L1 and L2, lack a 90-amino acid domain at their globular ‘tail’ region, but bear homology at the alpha-helical domain [ 57 , 58 ]. Another coiled-coil domain containing protein is the INM protein Esc1 of S. cerevisiae , which is involved in anchoring of telomeres [ 59 ]; over-expression of Esc1 produces abnormally long extensions of the NE [ 41 , 60 ]. While Esc1 is restricted to Saccharomycetes, the S. cerevisiae proteins Ebp2 and Rrs1 falling in this group are universally conserved and have key roles in anchoring and clustering of telomeric heterochromatin, and in ribosome biogenesis [ 61 , 62 ].…”

“…Heh1 contributes to NPC stability by interacting with membrane nucleoporins (nups) such as Pom152 at the NE lumen [ 76 ]. Loss of HEH1 does not cause any NE deformations and nuclei remain spherical, although are larger in size [ 41 , 77 ]. In S. pombe , LEM domain proteins Lem2, Man1 and Ima1 are involved in heterochromatin silencing at rDNA, centromeric and telomeric loci [ 69 ].…”

“…Abnormal structures of the NE in association with nucleolus have been seen in fungi [ 41 , 129 , 137 , 138 ] as well as plants [ 21 ]. However, an association between abnormal nucleolar domain and dysregulated lipid metabolism has been reported only in S. cerevisiae but not plants [ 41 ].…”

“…Abnormal structures of the NE in association with nucleolus have been seen in fungi [ 41 , 129 , 137 , 138 ] as well as plants [ 21 ]. However, an association between abnormal nucleolar domain and dysregulated lipid metabolism has been reported only in S. cerevisiae but not plants [ 41 ]. Interestingly, nuclear flares in fission yeast S. pombe and Schizosaccharomyces japonicus are not found in association with nucleolus [ 128 ].…”