MicroRNAs in kidney transplantation

Abstract

The discovery of novel classes of non-coding RNAs (ncRNAs) has revolutionized medicine. Long thought to be a mere cellular housekeeper, surprising functions have recently been uncovered. MicroRNAs (miRNAs), are a representative of the class of short ncRNAs, play a fundamental role in the control of DNA and protein biosynthesis and activity as well as pathology. Currently, miRNAs are being investigated as diagnostic and prognostic markers and potential therapeutic targets in kidney transplantation for such indolent processes as ischaemia-reperfusion injury, humoral rejection or viral infections. It is realistic to believe that monitoring of renal allograft recipients in the future will include genome-wide miRNA profiling of biological fluids. Based on these individual profiles, an informed decision on therapeutic consequences will be possible. A first success with a specific suppression of miRNAs by antisense oligonucleotides was achieved in experimental studies of reperfusion injury and humoral rejection. Proof of this concept in men comes from studies in such indolent viral infections as Ebola and hepatitis C, where anti-miR therapy led to sustained viral clearance. In this review, we summarize the basis of the recent ncRNA revolution and its implication for kidney transplantation.

Keywords: acute kidney injury; biomarker; miRNAs; rejection; renal transplantation.

Figure 1. Biogenesis and Function of miRNAs

Briefly, the primary transcript is transcribed and further processed into the precursor miRNA (pre-RNA) by Drosha, a RNase III enzyme in the nucleus. After export to the cytoplasm, Dicer (another RNase III enzyme) cleaves off the loop of the hairpin and generates a double-stranded RNA. Subsequently the mature miRNA strand binds to a member of the AGO protein family together with Dicer and a dsRNA-binding domain protein such as TRBP building the RNA-induced silencing complex (miRISC)). After mRNA target binding the miRISC complex induce mRNA target degradation or inhibition of protein translation.

Figure 2

Protein interaction network of experimentally verified targets of miR-182 (black) and their interaction partners (grey). Targets of miR-182 were extracted from miRTarBase (http://mirtarbase.mbc.nctu.edu.tw/) and are supported by strong experimental evidence (reporter assay or Western Blot). Blue edges: pathway interaction; pink edges: physical interaction. Network was created in Cytocape 2.8.1 with the GeneMANIA plugin (www.genemania.org).