PubMed · 9742633
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A M Kremenetskaia, I A Vorob'ev, Iu V Sidorova, A I Zakharova, N E Shklovskiĭ-Kordi, A I Vorob'ev. 1998. [Lymphocyte morphology].. https://pubmed.ncbi.nlm.nih.gov/9742633/
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The nucleolus is essential for ribosome biogenesis and cellular homeostasis, and its dysfunction can induce nucleolar stress, a process implicated in cancer and other diseases. However, nucleolar stress is commonly inferred from morphological changes or a limited set of functional assays, and quantitative approaches based on gene expression profiles remain lacking. Here, we integrate literature curation with multi-dataset screening to define a nucleolar stress gene signature and develop a nucleolar stress score (NuS) applicable to bulk transcriptomics, single-cell transcriptomics, proteomics, and spatial transcriptomics. Using this framework, we show in colorectal cancer models that oxaliplatin induces nucleolar stress, suppresses nascent rRNA synthesis, and activates p53 signaling, whereas these responses are attenuated in oxaliplatin-resistant cells. Combined with a ribosome biogenesis activity score (RiboSis), NuS captures related but distinct dimensions of nucleolar function and stratifies tumors into functional states associated with clinical outcomes. NuS-based analysis of perturbational transcriptomes further prioritizes compounds with putative nucleolar stress-inducing activity. Collectively, this study provides a quantitative framework for evaluating nucleolar stress and illustrates its applications in disease stratification and drug mechanism discovery.
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The incidence of micronucleoli in the course of terminal differentiation of human erythroblasts was studied by the cytochemical procedures for demonstration of RNA and characteristic proteins of interphase AgNORs. The last dividing stages of the erythroid lineage--polychromatophylic erythroblasts--characterized by the presence of micronucleoli exhibited significantly larger values of the nucleolar coefficient in specimens stained for AgNOR proteins than in those stained for RNA. In addition, both these and terminal non-dividing nucleated stages of the erythroid lineage--orthochromatic erythroblasts--possessed micronucleoli after staining for RNA in a much smaller percentage of cells than after staining for AgNOR proteins. Thus, both these observations indicate that micronucleoli in the course of terminal maturation of erythroblasts apparently lose the nucleolar RNA detectable by the light microscopic cytochemistry. In addition, silver-stained micronucleoli--nucleolar remnants--were also noted in erythroblasts expelling the nucleus.