Daughter-cell-specific modulation of nuclear pore complexes controls cell cycle entry during asymmetric division

Kumar, Arun; Sharma, Priyanka; Gomar-Alba, Mercè; Shcheprova, Zhanna; Daulny, Anne; Sanmartín, Trinidad; Matucci, Irene; Funaya, Charlotta; Beato, Miguel; Mendoza, Manuel

doi:10.1038/s41556-018-0056-9

Cited by 38 publications

(73 citation statements)

References 69 publications

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“…(Rb protein in humans) (Kumar et al, 2018). Our data in the FXR1-deficient cells show accumulation of cells with phosphorylated nuclear Rb (P-Rb) ( Figure 7E, F), which supports the speculation that FXR1-dependent G1 regulation could be due to specific effects on P-Rb export.…”

Section: Discussionsupporting

confidence: 84%

Spatial control of nucleoporin assembly by Fragile X-related proteins

Agote-Arán

Schmucker

Jeřábková

et al. 2019

Preprint

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HighlightsCytoplasmic nucleoporins are assembled by Fragile X-related (FXR) proteins and dynein FXR-Dynein pathway downregulation induces aberrant cytoplasmic aggregation of nucleoporins Cellular models of Fragile X syndrome accumulate aberrant cytoplasmic nucleoporin aggregates. FXR-Dynein pathway regulates nuclear morphology and G1 cell cycle progression eTOC Blurb Nucleoporins (Nups) form Nuclear Pore Complexes (NPCs) at the nuclear envelope. Agote-Arán at al. show how cells inhibit aberrant assembly of Nups in the cytoplasm and identify Fragile X-related (FXR) proteins and dynein that facilitate localization of Nups to the nuclear envelope and control G1 cell cycle progression. Summary Nucleoporins (Nups) build highly organized Nuclear Pore Complexes (NPCs) at the nuclear envelope (NE). Several Nups assemble into a sieve-like hydrogel within the central channel of the NPCs to regulate nucleocytoplasmic exchange. In the cytoplasm, a large excess of soluble Nups has been reported, but how their assembly is restricted to the NE is currently unknown. Here we show that Fragile X-related protein 1 (FXR1) can interact with several Nups and facilitate their localization to the NE during interphase through a microtubule and dyneindependent mechanism. Downregulation of FXR1 or closely related orthologs FXR2 and Fragile X mental retardation protein (FMRP) leads to the accumulation of cytoplasmic Nup protein condensates. Likewise, several models of Fragile X syndrome (FXS), characterized by a loss of FMRP, also accumulate cytoplasmic Nup aggregates. These aggregate-containing cells display aberrant nuclear morphology and a delay in G1 cell cycle progression. Our results reveal an unexpected role for the FXR protein family and dynein in the spatial regulation of nucleoporin assembly.

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Section: Discussionsupporting

confidence: 84%

Spatial control of nucleoporin assembly by Fragile X-related proteins

Agote-Arán

Schmucker

Jeřábková

et al. 2019

Preprint

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“…Hos3 binds to the daughter-cell side of the septin ring, a cytoskeletal structure that assembles at the bud neck (Wang and Collins, 2014). Hos3 then transiently associates with the periphery of the daughter cell nucleus during anaphase chromosome segregation (Kumar et al, 2018). Since the yeast NE does not disassemble during mitosis, NPCs destined to the bud are in close proximity with the bud neck during anaphase.…”

Section: Nuclear Pore Deacetylation Regulates Gene Expression In Buddmentioning

confidence: 99%

“…Recent work from our laboratory revealed that in budding yeast, an enzyme that deacetylates nuclear pore complexes acts as a cell fate determinant in daughter cells (Kumar et al, 2018). Nuclear pore complexes (NPCs) are multi-protein assemblies that forms channels in the nuclear envelope thus connecting the nucleus and cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Cell Identity by Modification of Nuclear Pore Complexes

Gomar-Alba

Mendoza

2020

Front. Genet.

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Nuclear pore complexes (NPCs) are protein assemblies that form channels across the nuclear envelope to mediate communication between the nucleus and the cytoplasm. Additionally, NPCs interact with chromatin and influence the position and expression of multiple genes. Interestingly, the composition of NPCs can vary in different cell-types, tissues, and developmental states. Here, we review recent findings suggesting that modifications of NPC composition, including post-translational modifications, play an instructive role in cell fate establishment. In particular, we focus on the role of cell-specific NPC deacetylation in asymmetrically dividing budding yeast, which modulates transport-dependent and transport-independent NPC functions to determine the time of commitment to a new division cycle in daughter cells. By modulating protein localization and gene expression, NPCs are therefore emerging as central regulators of cell identity.

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“…On one hand, artificial tethering of reporter genes to subtelomeric regions and to the nuclear periphery can lead to their silencing [16][17][18][19]. Moreover, perinuclear tethering of the CLN2 cyclin gene in daughter cells mediates its silencing during the G1 phase [20]. The association of silent information regulators (SIR) factors with telomeres also contributes to perinuclear repression [19].…”

Section: Introductionmentioning

confidence: 99%

Impact of chromosome fusions on 3D genome organization and gene expression in budding yeast

Stefano¹,

Giovanni

Baù

et al. 2017

Preprint

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The three-dimensional organization of chromosomes can influence transcription.However, the frequency and magnitude of these effects is still controversial. To determine how changes in chromosome positioning affect transcription across thousands of genes with minimal perturbation, we characterized nuclear organization and global gene expression in budding yeast containing growth-rate neutral chromosome fusions. We used computational modelling and single cell imaging to determine chromosome position and integrated these data with genome-wide transcriptional profiles from RNA sequencing. Chromosome displacement relative to the nuclear periphery has mild but widespread and significant effects on transcription. A 10% decrease in the time a gene spends near the nuclear periphery leads to a 10% increase in gene expression. Our study shows that basal transcriptional activity is sensitive to radial changes on chromosomal position, and provides support for the functional relevance of budding yeast chromosomelevel three-dimensional organization in gene expression.

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Daughter-cell-specific modulation of nuclear pore complexes controls cell cycle entry during asymmetric division

Cited by 38 publications

References 69 publications

Spatial control of nucleoporin assembly by Fragile X-related proteins

Spatial control of nucleoporin assembly by Fragile X-related proteins

Modulation of Cell Identity by Modification of Nuclear Pore Complexes

Impact of chromosome fusions on 3D genome organization and gene expression in budding yeast

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