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RNA 结合蛋白及其在肾脏疾病中的作用。

RNA-binding proteins and their role in kidney disease.

机构信息

Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

CECAD, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

出版信息

Nat Rev Nephrol. 2022 Mar;18(3):153-170. doi: 10.1038/s41581-021-00497-1. Epub 2021 Nov 3.

Abstract

RNA-binding proteins (RBPs) are of fundamental importance for post-transcriptional gene regulation and protein synthesis. They are required for pre-mRNA processing and for RNA transport, degradation and translation into protein, and can regulate every step in the life cycle of their RNA targets. In addition, RBP function can be modulated by RNA binding. RBPs also participate in the formation of ribonucleoprotein complexes that build up macromolecular machineries such as the ribosome and spliceosome. Although most research has focused on mRNA-binding proteins, non-coding RNAs are also regulated and sequestered by RBPs. Functional defects and changes in the expression levels of RBPs have been implicated in numerous diseases, including neurological disorders, muscular atrophy and cancers. RBPs also contribute to a wide spectrum of kidney disorders. For example, human antigen R has been reported to have a renoprotective function in acute kidney injury (AKI) but might also contribute to the development of glomerulosclerosis, tubulointerstitial fibrosis and diabetic kidney disease (DKD), loss of bicaudal C is associated with cystic kidney diseases and Y-box binding protein 1 has been implicated in the pathogenesis of AKI, DKD and glomerular disorders. Increasing data suggest that the modulation of RBPs and their interactions with RNA targets could be promising therapeutic strategies for kidney diseases.

摘要

RNA 结合蛋白(RBPs)在转录后基因调控和蛋白质合成中具有重要作用。它们参与前体 mRNA 的加工以及 RNA 的运输、降解和翻译为蛋白质,并可以调节其 RNA 靶标的生命周期中的每一个步骤。此外,RNA 结合可以调节 RBP 的功能。RBP 还参与核糖核蛋白复合物的形成,这些复合物构建了核糖体和剪接体等大分子机器。尽管大多数研究都集中在 mRNA 结合蛋白上,但非编码 RNA 也受到 RBPs 的调节和隔离。RBPs 的功能缺陷和表达水平的变化与许多疾病有关,包括神经退行性疾病、肌肉萎缩和癌症。RBPs 也与广泛的肾脏疾病有关。例如,已报道人抗原 R 在急性肾损伤(AKI)中具有肾保护功能,但也可能导致肾小球硬化、肾小管间质纤维化和糖尿病肾病(DKD),双尾 C 缺失与囊性肾病有关,Y 框结合蛋白 1 与 AKI、DKD 和肾小球疾病的发病机制有关。越来越多的数据表明,调节 RBPs 及其与 RNA 靶标的相互作用可能是治疗肾脏疾病的有前途的治疗策略。

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