Bressman Zachary J, Corbett Anita H, Ghalei Homa
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
Department of Biology, Emory College of Arts and Sciences, Atlanta, GA 30322, USA.
Philos Trans R Soc Lond B Biol Sci. 2025 Mar 6;380(1921):20230382. doi: 10.1098/rstb.2023.0382.
The RNA exosome is an essential, evolutionarily conserved ribonuclease required for processing and degradation of key cellular RNAs. The complex maintains RNA homeostasis within every cell by ensuring the proper maturation, quality control and turnover of various RNA species including rRNAs. A growing list of diseases, collectively termed RNA exosomopathies, are caused by mutations in genes encoding structural subunits of the RNA exosome complex. RNA exosomopathies often result in tissue-specific defects, particularly manifesting as neurological disorders, which is intriguing given the ubiquitous functions and expression of the RNA exosome. One such ubiquitous, essential function of the RNA exosome is its involvement in ribosome biogenesis. In this review, we discuss the established connections between the RNA exosome and ribosome biogenesis, exploring the potential mechanisms through which RNA exosomopathies could influence ribosome heterogeneity, leading to aberrant translation and pathogenesis. We highlight the critical need for research in this area that can aid in understanding the complex aetiology of RNA exosomopathies and the future development of therapeutic strategies to mitigate pathology.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.
RNA外切体是一种重要的、在进化上保守的核糖核酸酶，参与关键细胞RNA的加工和降解。该复合物通过确保包括rRNA在内的各种RNA种类的正确成熟、质量控制和周转，维持每个细胞内的RNA稳态。越来越多的疾病（统称为RNA外切体病）是由编码RNA外切体复合物结构亚基的基因突变引起的。RNA外切体病常导致组织特异性缺陷，尤其表现为神经疾病，鉴于RNA外切体的普遍功能和表达，这一点颇具吸引力。RNA外切体的一个如此普遍且重要的功能是其参与核糖体生物发生。在这篇综述中，我们讨论了RNA外切体与核糖体生物发生之间已确立的联系，探讨了RNA外切体病可能影响核糖体异质性从而导致异常翻译和发病机制的潜在机制。我们强调了该领域研究的迫切需求，这有助于理解RNA外切体病的复杂病因以及未来减轻病理的治疗策略的发展。本文是“核糖体多样性及其对蛋白质合成、发育和疾病的影响”讨论会议特刊的一部分。
