Department of Genetics, Yale School of Medicine, New Haven, CT, U.S.A.
Biosci Rep. 2023 Jul 26;43(7). doi: 10.1042/BSR20230631.
Ribosome biogenesis is the complex and essential process that ultimately leads to the synthesis of cellular proteins. Understanding each step of this essential process is imperative to increase our understanding of basic biology, but also more critically, to provide novel therapeutic avenues for genetic and developmental diseases such as ribosomopathies and cancers which can arise when this process is impaired. In recent years, significant advances in technology have made identifying and characterizing novel human regulators of ribosome biogenesis via high-content, high-throughput screens. Additionally, screening platforms have been used to discover novel therapeutics for cancer. These screens have uncovered a wealth of knowledge regarding novel proteins involved in human ribosome biogenesis, from the regulation of the transcription of the ribosomal RNA to global protein synthesis. Specifically, comparing the discovered proteins in these screens showed interesting connections between large ribosomal subunit (LSU) maturation factors and earlier steps in ribosome biogenesis, as well as overall nucleolar integrity. In this review, a discussion of the current standing of screens for human ribosome biogenesis factors through the lens of comparing the datasets and discussing the biological implications of the areas of overlap will be combined with a look toward other technologies and how they can be adapted to discover more factors involved in ribosome synthesis, and answer other outstanding questions in the field.
核糖体生物发生是一个复杂而必要的过程，最终导致细胞蛋白质的合成。了解这个基本过程的每一步对于增加我们对基础生物学的理解是至关重要的，但更重要的是，为遗传和发育疾病（如核糖体病和癌症）提供新的治疗途径，当这个过程受损时，这些疾病就会发生。近年来，技术的重大进步使得通过高内涵、高通量筛选来鉴定和表征新型人类核糖体生物发生调节剂成为可能。此外，筛选平台也被用于发现癌症的新型治疗药物。这些筛选揭示了大量与人类核糖体生物发生相关的新型蛋白质的知识，从核糖体 RNA 的转录调控到全局蛋白质合成。具体来说，比较这些筛选中发现的蛋白质显示出大核糖体亚基（LSU）成熟因子与核糖体生物发生早期步骤以及整体核仁完整性之间的有趣联系。在这篇综述中，我们将通过比较数据集来讨论当前人类核糖体生物发生因子筛选的现状，并讨论重叠区域的生物学意义，同时还将着眼于其他技术以及如何对其进行改造以发现更多参与核糖体合成的因子，并回答该领域的其他悬而未决的问题。
