Cell autonomous and non-autonomous consequences of deviations in translation machinery on organism growth and the connecting signalling pathways.
Cell autonomous and non-autonomous consequences of deviations in translation machinery on organism growth and the connecting signalling pathways.
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作者：
翻译机器负责细胞蛋白质的生产；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会导致罕见的核糖体病，例如人类的戴蒙德-布莱克凡贫血和各种模式生物的类似发育缺陷。在特定肿瘤中也观察到翻译机器组件的体细胞拷贝数改变。生物体范围内对核糖体蛋白或翻译机器组件的单倍体功能不足突变的反应是复杂的：翻译机器的变化导致核糖体生物合成、蛋白质翻译减少以及蛋白质稳态和细胞信号传导途径的改变。通过细胞间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主和非自主地影响细胞。我们首先简要介绍模型生物，其中蛋白质合成和核糖体生物发生的突变体或敲低被表征。接下来，我们具体描述了在秀丽隐杆线虫和黑腹果蝇中的观察结果，其中一部分细胞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，我们介绍与核糖体生物合成/蛋白质合成机制相互作用的特征信号传导途径，重点关注它们在生物体发育过程中各自的功能。
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.
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DOI：
10.1038/s41576-020-0262-8
发表时间：
2020-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Baker NE
通讯作者：
Baker NE
影响因子：
56.9
作者：
BLACKWELL, TK;KRETZNER, L;WEINTRAUB, H
通讯作者：
WEINTRAUB, H
影响因子：
11.8
作者：
Boulan, Laura;Andersen, Ditte;Leopold, Pierre
通讯作者：
Leopold, Pierre
种系RPS20突变表型的膨胀，包括钻石 - 黑色贫血。
影响因子：
3.9
作者：
Bhar S;Zhou F;Reineke LC;Morris DK;Khincha PP;Giri N;Mirabello L;Bergstrom K;Lemon LD;Williams CL;Toh Y;Elghetany MT;Lloyd RE;Alter BP;Savage SA;Bertuch AA
通讯作者：
Bertuch AA
影响因子：
4.8
作者：
Biever A;Valjent E;Puighermanal E
通讯作者：
Puighermanal E