The nucleolar detention pathway

Audas, Timothy E.; Jacob, Mathieu D.; Lee, Stephen

doi:10.4161/cc.20140

Cited by 52 publications

(21 citation statements)

References 40 publications

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“…In mammalian cells rDNA intergenic transcripts accumulate in the nucleolus after heat shock and provoke the nucleolar sequestration of nuclear proteins like the DNA methyltransferase DNMT1, the proteasome factor SUG1, or POLD1, a key factor of DNA replication (Audas et al, 2012a, 2012b). A similar mechanism may exist to regulate transcription by a phenomenon that could be named transcriptional regulation by nucleolar sequestration.…”

Section: Discussionmentioning

confidence: 99%

Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome

et al. 2016

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The nucleolus is the site of ribosomal RNA (rRNA) gene transcription, rRNA processing and ribosome biogenesis. However, the nucleolus also plays additional roles in the cell. We isolated nucleoli by Fluorescence Activated Cell Sorting (FACS) and identified Nucleolus-Associated Chromatin Domains (NADs) by deep sequencing, comparing wild-type plants and null mutants for the nucleolar protein, NUCLEOLIN 1 (NUC1). NADs are primarily genomic regions with heterochromatic signatures and include transposable elements (TEs), sub-telomeric regions and mostly inactive protein-coding genes. However, NADs also include active ribosomal RNA genes, and the entire short arm of chromosome 4 adjacent to them. In nuc1 null mutants, which alter rRNA gene expression and overall nucleolar structure, NADs are altered, telomere association with the nucleolus is decreased and telomeres become shorter. Collectively, our studies reveal roles for NUC1 and the nucleolus in the spatial organization of chromosomes as well as telomere maintenance.

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Section: Discussionmentioning

confidence: 99%

Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome

et al. 2016

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“…Through the inactivation of molecular networks and the interruption of rRNA synthesis, the remodeled nucleolus likely contributes to cell viability under conditions of stress (Olson, 2004; Mayer and Grummt, 2005; Boulon et al. , 2010; Audas et al. , 2012b).…”

Section: Discussionmentioning

confidence: 99%

Environmental cues induce a long noncoding RNA–dependent remodeling of the nucleolus

Jacob

Audas

Uniacke

et al. 2013

MBoC

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105

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“…In addition, compositional and environmental changes beyond protein abundance can have a large effect on phase separation. Multiple lines of evidence suggest that the threshold for phase separation can be robustly regulated within the cell, implying that this may be important to execute specific biological functions 1528, 31–51,28,29, 30–33, 34 .…”

Section: Regulating Phase Separationmentioning

confidence: 99%

“…Prominent examples include the p53 inhibitor MDM2, which is sent to detention centers during p53 activation 30–33 , and VHL, which degrades HIF, the transcription factor responsible for regulating the cellular response to hypoxia. Here aggregation is seeded not by general interactions with nucleic acid, but rather by sequence-specific interactions with ribosomal intergenic spacer long non-coding RNAs 71–74 .…”

Section: Regulating Phase Separationmentioning

confidence: 99%

It Pays To Be in Phase

2018

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To survive, organisms must orchestrate many competing biochemical and regulatory processes in time and space. Recent work has suggested that the underlying chemical properties of some biomolecules allow them to self-organize, and that life may have exploited this property to organize biochemistry in space and time within cells. Such phase separation is ubiquitous, particularly among the many regulatory proteins that harbor prion-like intrinsically disordered domains. And yet, despite evident regulation by post-translational modification and myriad other stimuli, the biological significance of many phase-separated compartments remains uncertain. Many potential functions have been proposed but far fewer have been demonstrated. A burgeoning subfield at the intersection of cell biology and polymer physics has defined the biophysical underpinnings that govern the genesis and stability of these particles. The picture is complex: many assemblies are composed of multiple proteins that each have the capacity to phase separate. Here, we briefly discuss this foundational work and survey recent efforts combining targeted biochemical perturbations and quantitative modeling to specifically address the diverse roles that phase separation processes may play in biology.

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The nucleolar detention pathway

Cited by 52 publications

References 40 publications

Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome

Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome

Environmental cues induce a long noncoding RNA–dependent remodeling of the nucleolus

It Pays To Be in Phase

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