Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
Open Biol. 2022 Apr;12(4):210308. doi: 10.1098/rsob.210308. Epub 2022 Apr 27.
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 and , 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.
翻译机器负责细胞蛋白的生成；因此，细胞将其大部分资源用于核糖体的生物发生和蛋白质合成。翻译机器成分的单拷贝功能丧失会导致罕见的核糖体病，如人类的 Diamond-Blackfan 贫血和各种模式生物的类似发育缺陷。在特定的肿瘤中也观察到翻译机器成分的体细胞拷贝数改变。核糖体蛋白或翻译机器成分的功能不全缺失突变的全生物体反应是复杂的：翻译机器的变化导致核糖体生物发生、蛋白质翻译和蛋白质动态平衡以及细胞信号通路的改变减少。通过细胞间相互作用和分泌激素，细胞受到翻译机器或核糖体生物发生变化的自主和非自主影响。我们首先简要介绍了蛋白质合成和核糖体生物发生的突变体或敲低特征的模式生物。接下来，我们特别描述了在 和 中的观察结果，其中细胞子集的蛋白质合成不足会触发非自主的细胞生长或凋亡反应，从而影响附近的细胞和组织。然后，我们介绍了与核糖体生物发生/蛋白质合成机器相互作用的特征信号通路，并强调了它们在生物体发育过程中的各自功能。
