Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla, Consejo Superior de Investigaciones Científicas, Junta de Andalucía, Universidad Pablo de Olavide, 41092 Seville, Spain; Departamento de Bioquímica Vegetal y Biología Molecular, Universidad de Sevilla, 41012 Seville, Spain.
Biochim Biophys Acta Gene Regul Mech. 2024 Jun;1867(2):195029. doi: 10.1016/j.bbagrm.2024.195029. Epub 2024 Apr 19.
The perception that the nucleoli are merely the organelles where ribosome biogenesis occurs is challenged. Only around 30 % of nucleolar proteins are solely involved in producing ribosomes. Instead, the nucleolus plays a critical role in controlling protein trafficking during stress and, according to its dynamic nature, undergoes continuous protein exchange with nucleoplasm under various cellular stressors. Hence, the concept of nucleolar stress has evolved as cellular insults that disrupt the structure and function of the nucleolus. Considering the emerging role of this organelle in DNA repair and the fact that rDNAs are the most fragile genomic loci, therapies targeting the nucleoli are increasingly being developed. Besides, drugs that target ribosome synthesis and induce nucleolar stress can be used in cancer therapy. In contrast, agents that regulate nucleolar activity may be a potential treatment for neurodegeneration caused by abnormal protein accumulation in the nucleolus. Here, I explore the roles of nucleoli beyond their ribosomal functions, highlighting the factors triggering nucleolar stress and their impact on genomic stability.
人们认为核仁仅仅是核糖体生物发生的细胞器，但这种观点受到了挑战。只有大约 30%的核仁蛋白仅参与核糖体的生成。相反，核仁在应激时控制蛋白质运输中起着关键作用，并且根据其动态性质，在各种细胞应激下与核质进行持续的蛋白质交换。因此，核仁应激的概念已经发展成为破坏核仁结构和功能的细胞损伤。考虑到这个细胞器在 DNA 修复中的新兴作用，以及 rDNA 是最脆弱的基因组位点这一事实，针对核仁的治疗方法正在不断被开发。此外，靶向核糖体合成并诱导核仁应激的药物可用于癌症治疗。相反，调节核仁活性的药物可能是治疗核仁中异常蛋白质积累引起的神经退行性变的潜在方法。在这里，我探讨了核仁超越核糖体功能的作用，强调了触发核仁应激的因素及其对基因组稳定性的影响。
