Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
Escuela de Doctorado y Estudios de Postgrado, Universidad de La Laguna, 38200 Tenerife, Spain.
Cells. 2019 Jul 26;8(8):779. doi: 10.3390/cells8080779.
Once thought a mere ribosome factory, the nucleolus has been viewed in recent years as an extremely sensitive gauge of diverse cellular stresses. Emerging concepts in nucleolar biology include the nucleolar stress response (NSR), whereby a series of cell insults have a special impact on the nucleolus. These insults include, among others, ultra-violet radiation (UV), nutrient deprivation, hypoxia and thermal stress. While these stresses might influence nucleolar biology directly or indirectly, other perturbances whose origin resides in the nucleolar biology also trigger nucleolar and systemic stress responses. Among the latter, we find mutations in nucleolar and ribosomal proteins, ribosomal RNA (rRNA) processing inhibitors and ribosomal DNA (rDNA) transcription inhibition. The p53 protein also mediates NSR, leading ultimately to cell cycle arrest, apoptosis, senescence or differentiation. Hence, NSR is gaining importance in cancer biology. The nucleolar size and ribosome biogenesis, and how they connect with the Target of Rapamycin (TOR) signalling pathway, are also becoming important in the biology of aging and cancer. Simple model organisms like the budding yeast , easy to manipulate genetically, are useful in order to study nucleolar and rDNA structure and their relationship with stress. In this review, we summarize the most important findings related to this topic.
核仁曾一度被认为只是核糖体的工厂，但近年来，它被视为细胞应对各种压力的极其敏感的指标。核仁生物学中的新兴概念包括核仁应激反应（NSR），即一系列细胞损伤对核仁有特殊影响。这些损伤包括紫外线（UV）辐射、营养剥夺、缺氧和热应激等。虽然这些压力可能直接或间接地影响核仁生物学，但核仁生物学中起源的其他干扰也会引发核仁及全身性应激反应。后者包括核仁蛋白和核糖体蛋白、核糖体 RNA（rRNA）加工抑制剂和核糖体 DNA（rDNA）转录抑制的突变。p53 蛋白也介导 NSR，最终导致细胞周期停滞、细胞凋亡、衰老或分化。因此，NSR 在癌症生物学中变得越来越重要。核仁大小和核糖体生物发生，以及它们与雷帕霉素（TOR）信号通路的联系，在衰老和癌症生物学中也变得越来越重要。简单的模式生物，如易于遗传操作的 budding yeast，对于研究核仁及 rDNA 结构及其与应激的关系非常有用。在这篇综述中，我们总结了与这一主题相关的最重要的发现。
