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RNA-binding proteins and their role in kidney disease

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NATURE REVIEWS NEPHROLOGY
卷 18, 期 3, 页码 153-170

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NATURE PORTFOLIO
DOI: 10.1038/s41581-021-00497-1

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RNA-binding proteins play crucial roles in the RNA life cycle and are implicated in various diseases, including kidney disorders. Modulation of RBPs and their interactions with RNA targets present promising therapeutic strategies for kidney diseases.
RNA-binding proteins are involved in every stage of the RNA life cycle and have a major impact on cellular biology. Here, the authors discuss current knowledge of RNA-binding proteins, their interactions with RNAs and proteins, their roles in kidney diseases and their potential as novel therapeutic targets. 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.

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