Department of Molecular Biology, University Medical Center Göttingen, Göttingen, Germany.
Göttingen Center for Molecular Biosciences, Georg-August University, Göttingen, Germany.
EMBO J. 2019 Jul 1;38(13):e100278. doi: 10.15252/embj.2018100278. Epub 2019 May 14.
The essential cellular process of ribosome biogenesis is at the nexus of various signalling pathways that coordinate protein synthesis with cellular growth and proliferation. The fact that numerous diseases are caused by defects in ribosome assembly underscores the importance of obtaining a detailed understanding of this pathway. Studies in yeast have provided a wealth of information about the fundamental principles of ribosome assembly, and although many features are conserved throughout eukaryotes, the larger size of human (pre-)ribosomes, as well as the evolution of additional regulatory networks that can modulate ribosome assembly and function, have resulted in a more complex assembly pathway in humans. Notably, many ribosome biogenesis factors conserved from yeast appear to have subtly different or additional functions in humans. In addition, recent genome-wide, RNAi-based screens have identified a plethora of novel factors required for human ribosome biogenesis. In this review, we discuss key aspects of human ribosome production, highlighting differences to yeast, links to disease, as well as emerging concepts such as extra-ribosomal functions of ribosomal proteins and ribosome heterogeneity.
核糖体生物发生是细胞的基本过程,处于各种信号通路的交汇点,这些信号通路协调蛋白质合成与细胞生长和增殖。大量疾病是由于核糖体组装缺陷引起的,这一事实突出了详细了解这一途径的重要性。酵母的研究为核糖体组装的基本原理提供了丰富的信息,尽管真核生物中许多特征都是保守的,但人类(前)核糖体的体积更大,以及额外的调节网络的进化可以调节核糖体的组装和功能,导致人类的组装途径更加复杂。值得注意的是,许多从酵母中保守的核糖体生物发生因子在人类中似乎具有微妙不同或额外的功能。此外,最近基于全基因组的 RNAi 筛选已经确定了大量人类核糖体生物发生所必需的新因子。在这篇综述中,我们讨论了人类核糖体产生的关键方面,强调了与酵母的差异、与疾病的联系,以及核糖体蛋白和核糖体异质性的额外核糖体功能等新兴概念。