PDF(Pubmed)
Abstract：
Translation machinery is responsible for the production of cellular proteins; thus, cells devote the majority of their resources to ribosome biogenesis and protein synthesis. Single-copy loss of function in the translation machinery components results in rare ribosomopathy disorders, such as Diamond-Blackfan anaemia in humans and similar developmental defects in various model organisms. Somatic copy number alterations of translation machinery components are also observed in specific tumours. The organism-wide response to haploinsufficient loss-of-function mutations in ribosomal proteins or translation machinery components is complex: variations in translation machinery lead to reduced ribosome biogenesis, protein translation and altered protein homeostasis and cellular signalling pathways. Cells are affected both autonomously and non-autonomously by changes in translation machinery or ribosome biogenesis through cell-cell interactions and secreted hormones. We first briefly introduce the model organisms where mutants or knockdowns of protein synthesis and ribosome biogenesis are characterized. Next, we specifically describe observations in Caenorhabditis elegans and Drosophila melanogaster, where insufficient protein synthesis in a subset of cells triggers cell non-autonomous growth or apoptosis responses that affect nearby cells and tissues. We then cover the characterized signalling pathways that interact with ribosome biogenesis/protein synthesis machinery with an emphasis on their respective functions during organism development.
摘要：
翻译机器负责细胞蛋白质的产生；因此，细胞将大部分资源用于核糖体生物发生和蛋白质合成。翻译机器组件中的单拷贝功能丧失导致罕见核糖体病，例如人类的Diamond-Blackfan贫血和各种模式生物的类似发育缺陷。在特定肿瘤中还观察到翻译机器组件的体细胞拷贝数改变。生物体对核糖体蛋白或翻译机制成分中单倍体功能缺失突变的反应是复杂的：翻译机制的变化导致核糖体生物发生减少，蛋白质翻译和改变的蛋白质稳态和细胞信号通路。通过细胞-细胞相互作用和分泌的激素，翻译机制或核糖体生物发生的变化会自动和非自动地影响细胞。我们首先简要介绍了模型生物，其中表征了蛋白质合成和核糖体生物发生的突变体或敲除。接下来,我们特别描述了秀丽隐杆线虫和黑腹果蝇的观察结果，其中细胞亚群中蛋白质合成不足会触发细胞非自主生长或凋亡反应，从而影响附近的细胞和组织。然后，我们涵盖了与核糖体生物发生/蛋白质合成机制相互作用的特征性信号通路，并强调了它们在生物体发育过程中的各自功能。
