Nuclear Organization in Response to Stress: A Special Focus on Nucleoli

Batnasan, Enkhzaya; Koivukoski, Sonja; Kärkkäinen, Minttu; Latonen, Leena

doi:10.1007/978-3-031-06573-6_17

Cited by 4 publications

(2 citation statements)

References 121 publications

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“…Investigations of the rDNA chromatin state, enabled by the recent complete annotation of the human genome [ 85 ], point to UBF (upstream-binding factor) as being bound throughout the cell cycle and as being a key to nucleolar reformation following mitosis [ 86 ]. Additionally, studies of rDNA chromatin are revealing its role in nucleolar morphology and function across cell types and cell states [ 54 , 87–89 ]. For example, evidence from different hematopoietic cells that range in ribosomal output by over an order of magnitude suggests that larger FC sizes and a specific chromatin landscape at NORs are correlated with increased ribosomal outputs [ 58 , 59 , 90 ].…”

Section: Nucleolar Sub-phases Are Defined By Distinct Macromolecular ...mentioning

confidence: 99%

Emergent microenvironments of nucleoli

King,

Ruff,

Pappu

2024

Nucleus

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In higher eukaryotes, the nucleolus harbors at least three sub-phases that facilitate multiple functionalities including ribosome biogenesis. The three prominent coexisting sub-phases are the fibrillar center (FC), the dense fibrillar component (DFC), and the granular component (GC). Here, we review recent efforts in profiling sub-phase compositions that shed light on the types of physicochemical properties that emerge from compositional biases and territorial organization of specific types of macromolecules. We highlight roles played by molecular grammars which refers to protein sequence features including the substrate binding domains, the sequence features of intrinsically disordered regions, and the multivalence of these distinct types of domains / regions. We introduce the concept of a barcode of emergent physicochemical properties of nucleoli. Although our knowledge of the full barcode remains incomplete, we hope that the concept prompts investigations into undiscovered emergent properties and engenders an appreciation for how and why unique microenvironments control biochemical reactions

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Section: Nucleolar Sub-phases Are Defined By Distinct Macromolecular ...mentioning

confidence: 99%

Emergent microenvironments of nucleoli

King,

Ruff,

Pappu

2024

Nucleus

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“…Nucleolar stress reflects inhibition of transcription by RNA polymerase I and downregulation of ribosome synthesis, evidenced by a decrease in transcription of ribosomal genes, dispersal of the nucleolar components to nucleoplasm, translocation of many factors to nucleoli, and formation of nucleolar caps in the outer surface of the nucleoli facing nucleoplasm [ 1 , 13 , 25 ]. Nucleolar stress can be monitored through translocation of NPM to nucleoplasm, reflecting the dispersal of the phase-separated nucleolar structures following inhibition [ 3 , 4 , 10 , 12 , 17 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Platinum-based drugs induce phenotypic alterations in nucleoli and Cajal bodies in prostate cancer cells

Batnasan,

Kärkkäinen,

Koivukoski

et al. 2024

Cancer Cell Int

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Purpose Platinum-based drugs are cytotoxic drugs commonly used in cancer treatment. They cause DNA damage, effects of which on chromatin and cellular responses are relatively well described. Yet, the nuclear stress responses related to RNA processing are incompletely known and may be relevant for the heterogeneity with which cancer cells respond to these drugs. Here, we determine the type and extent of nuclear stress responses of prostate cancer cells to clinically relevant platinum drugs. Methods We study nucleolar and Cajal body (CB) responses to cisplatin, carboplatin, and oxaliplatin with immunofluorescence-based methods in prostate cancer cells. We utilize organelle-specific markers NPM, Fibrillarin, Coilin, and SMN1, and study CB-regulatory proteins FUS and TDP-43 using siRNA-mediated downregulation. Results Different types of prostate cancer cells have different sensitivities to platinum drugs. With equally cytotoxic doses, cisplatin, and oxaliplatin induce prominent nucleolar and CB stress responses while the nuclear stress phenotypes to carboplatin are milder. We find that Coilin is a stress-specific marker for platinum drug response heterogeneity. We also find that CB-associated, stress-responsive RNA binding proteins FUS and TDP-43 control Coilin and CB biology in prostate cancer cells and, further, that TDP-43 is associated with stress-responsive CBs in prostate cancer cells. Conclusion Our findings provide insight into the heterologous responses of prostate cancer cells to different platinum drug treatments and indicate Coilin and TDP-43 as stress mediators in the varied outcomes. These results help understand cancer drug responses at a cellular level and have implications in tackling heterogeneity in cancer treatment outcomes.

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Epigenetic modifications of 45S rDNA associates with the disruption of nucleolar organisation during Cd stress response in Pakchoi

Xiang,

Zhang,

et al. 2024

Ecotoxicology and Environmental Safety

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Nuclear Organization in Response to Stress: A Special Focus on Nucleoli

Cited by 4 publications

References 121 publications

Emergent microenvironments of nucleoli

Emergent microenvironments of nucleoli

Platinum-based drugs induce phenotypic alterations in nucleoli and Cajal bodies in prostate cancer cells

Epigenetic modifications of 45S rDNA associates with the disruption of nucleolar organisation during Cd stress response in Pakchoi

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