Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University, 07745 Jena, Germany; email:
Leibniz-Institute on Aging-Fritz Lipmann Institute, 07745 Jena, Germany.
Annu Rev Biochem. 2018 Jun 20;87:51-73. doi: 10.1146/annurev-biochem-062917-012612. Epub 2018 Mar 28.
Ribosome biogenesis is a complex and highly energy-demanding process that requires the concerted action of all three nuclear RNA polymerases (Pol I-III) in eukaryotes. The three largest ribosomal RNAs (rRNAs) originate from a precursor transcript (pre-rRNA) that is encoded by multicopy genes located in the nucleolus. Transcription of these rRNA genes (rDNA) by Pol I is the key regulation step in ribosome production and is tightly controlled by an intricate network of signaling pathways and epigenetic mechanisms. In this article, we give an overview of the composition of the basal Pol I machinery and rDNA chromatin. We discuss rRNA gene regulation in response to environmental signals and developmental cues and focus on perturbations occurring in diseases linked to either excessive or limited rRNA levels. Finally, we discuss the emerging view that rDNA integrity and activity may be involved in the aging process.
核糖体生物发生是一个复杂且高度耗能的过程，需要真核生物中所有三种核 RNA 聚合酶（Pol I-III）的协同作用。三种最大的核糖体 RNA（rRNA）来源于前体转录本（pre-rRNA），该转录本由位于核仁中的多拷贝基因编码。Pol I 对这些 rRNA 基因（rDNA）的转录是核糖体产生的关键调节步骤，受信号通路和表观遗传机制的复杂网络的严格控制。在本文中，我们概述了基本的 Pol I 机器和 rDNA 染色质的组成。我们讨论了 rRNA 基因响应环境信号和发育线索的调节，并重点讨论了与 rRNA 水平过高或过低相关的疾病中发生的扰动。最后，我们讨论了 rDNA 完整性和活性可能与衰老过程有关的新观点。
