MicroRNAs in kidney development and disease
Débora Malta Cerqueira, … , Maliha Tayeb, Jacqueline Ho
Débora Malta Cerqueira, … , Maliha Tayeb, Jacqueline Ho
Published May 9, 2022
Citation Information: JCI Insight. 2022;7(9):e158277. https://doi.org/10.1172/jci.insight.158277.
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Review

MicroRNAs in kidney development and disease

Abstract

MicroRNAs (miRNAs) belong to a class of endogenous small noncoding RNAs that regulate gene expression at the posttranscriptional level, through both translational repression and mRNA destabilization. They are key regulators of kidney morphogenesis, modulating diverse biological processes in different renal cell lineages. Dysregulation of miRNA expression disrupts early kidney development and has been implicated in the pathogenesis of developmental kidney diseases. In this Review, we summarize current knowledge of miRNA biogenesis and function and discuss in detail the role of miRNAs in kidney morphogenesis and developmental kidney diseases, including congenital anomalies of the kidney and urinary tract and Wilms tumor. We conclude by discussing the utility of miRNAs as potentially novel biomarkers and therapeutic agents.

Authors

Débora Malta Cerqueira, Maliha Tayeb, Jacqueline Ho

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Figure 3

Mutations in miRNA-processing genes result in aberrant miRNA expression and Wilms tumorigenesis.

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Mutations in miRNA-processing genes result in aberrant miRNA expression ...
Recurrent mutations in a metal-binding (Mg2+) residue of the RNase IIIb domain of DROSHA (E1147K) or in the double-stranded RNA-binding domain of DGRC8 (E518K) disrupt the cleavage of pri-miRNAs into pre-miRNAs. Mutations in XPO5 (encodes exportin 5) prevent pre-miRNA export, which culminates in pre-miRNA accumulation in the nucleus. Frameshift mutations in TARBP2 (encodes TRBP) and mutations affecting the RNase IIIb domain of DICER1 can disrupt the processing of pre-miRNAs into mature miRNAs. In stem and progenitor cells, members of the let-7 miRNA family function as tumor suppressors, and their expression is tightly regulated by the RNA-binding protein Lin28. Lin28A binds to the terminal loop of let-7 precursors and recruits the activity of the terminal uridyl transferases TUT4/7 to produce uridylated pre-let-7, which is subsequently degraded by DIS3L2. Overexpression of LIN28 and mutations in DISL3L2 have been associated with aberrant mature let-7 expression and Wilms tumorigenesis. Created with BioRender.com.