Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
Int J Mol Sci. 2021 Jun 23;22(13):6759. doi: 10.3390/ijms22136759.
Nucleolar stress occurs when ribosome production or function declines. Nucleolar stress in stem cells or progenitor cells often leads to disease states called ribosomopathies. offers a robust system to explore how nucleolar stress causes cell cycle arrest, apoptosis, or autophagy depending on the cell type. We provide an overview of nucleolar stress in by depleting nucleolar phosphoprotein of 140 kDa (Nopp140), a ribosome biogenesis factor (RBF) in nucleoli and Cajal bodies (CBs). The depletion of Nopp140 in eye imaginal disc cells generates eye deformities reminiscent of craniofacial deformities associated with the Treacher Collins syndrome (TCS), a human ribosomopathy. We show the activation of c-Jun N-terminal Kinase (JNK) in larvae homozygous for a gene deletion. JNK is known to induce the expression of the pro-apoptotic Hid protein and autophagy factors Atg1, Atg18.1, and Atg8a; thus, JNK is a central regulator in nucleolar stress. Ribosome abundance declines upon Nopp140 loss, but unusual cytoplasmic granules accumulate that resemble Processing (P) bodies based on marker proteins, Decapping Protein 1 (DCP1) and Maternal expression at 31B (Me31B). Wild type brain neuroblasts (NBs) express copious amounts of endogenous coilin, but coilin levels decline upon nucleolar stress in most NB types relative to the Mushroom body (MB) NBs. MB NBs exhibit resilience against nucleolar stress as they maintain normal coilin, Deadpan, and EdU labeling levels.
核仁应激发生在核糖体生成或功能下降时。干细胞或祖细胞中的核仁应激通常会导致称为核仁病的疾病状态。秀丽隐杆线虫为探索核仁应激如何根据细胞类型导致细胞周期停滞、细胞凋亡或自噬提供了一个强大的系统。我们通过耗尽核仁磷蛋白 140kDa（Nopp140）来概述核仁应激，Nopp140 是核仁内和 Cajal 体（CB）中的核糖体生物发生因子（RBF）。眼盘细胞中 Nopp140 的耗竭会导致眼睛畸形，类似于与 Treacher Collins 综合征（TCS）相关的颅面畸形，TCS 是一种人类核仁病。我们显示出 JNK 在 基因缺失纯合子幼虫中的激活。众所周知，JNK 会诱导促凋亡 Hid 蛋白和自噬因子 Atg1、Atg18.1 和 Atg8a 的表达；因此，JNK 是 核仁应激的中心调节剂。Nopp140 缺失后核糖体丰度下降，但会积累不寻常的细胞质颗粒，这些颗粒基于标记蛋白 Decapping Protein 1（DCP1）和 Maternal expression at 31B（Me31B）类似于处理（P）体。野生型脑神经母细胞（NBs）表达大量内源性 coilin，但相对于蘑菇体（MB）NBs，大多数 NB 类型中的核仁应激会导致 coilin 水平下降。MB NBs 对核仁应激具有弹性，因为它们保持正常的 coilin、Deadpan 和 EdU 标记水平。
