Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, PO Box 12233 MD F3-05, Research Triangle Park, NC 27709, USA.
Cell Rep. 2018 Feb 13;22(7):1923-1934. doi: 10.1016/j.celrep.2018.01.056.
Ribosome biogenesis is a highly regulated, essential cellular process. Although studies in yeast have established some of the biological principles of ribosome biogenesis, many of the intricacies of its regulation in higher eukaryotes remain unknown. To understand how ribosome biogenesis is globally integrated in human cells, we conducted a genome-wide siRNA screen for regulators of nucleolar number. We found 139 proteins whose depletion changed the number of nucleoli per nucleus from 2-3 to only 1 in human MCF10A cells. Follow-up analyses on 20 hits found many (90%) to be essential for the nucleolar functions of rDNA transcription (7), pre-ribosomal RNA (pre-rRNA) processing (16), and/or global protein synthesis (14). This genome-wide analysis exploits the relationship between nucleolar number and function to discover diverse cellular pathways that regulate the making of ribosomes and paves the way for further exploration of the links between ribosome biogenesis and human disease.
核糖体生物发生是一个高度调控的、必不可少的细胞过程。尽管在酵母中的研究已经确立了核糖体生物发生的一些生物学原理，但在高等真核生物中，其调控的许多细节仍然未知。为了了解核糖体生物发生如何在人类细胞中被全局整合，我们进行了全基因组 siRNA 筛选，以寻找核仁数量的调节剂。我们发现了 139 种蛋白质，它们的消耗使每个核仁的核仁数量从 2-3 个减少到人类 MCF10A 细胞中的仅 1 个。对 20 个命中靶点的后续分析发现，其中许多（90%）对于 rDNA 转录（7）、pre-ribosomal RNA（pre-rRNA）加工（16）和/或全球蛋白质合成（14）的核仁功能至关重要。这项全基因组分析利用了核仁数量和功能之间的关系，发现了调节核糖体生成的多种细胞途径，并为进一步探索核糖体生物发生与人类疾病之间的联系铺平了道路。
