microRNAs in kidneys: biogenesis, regulation, and pathophysiological roles

Abstract

MicroRNAs (miRNA) are endogenously produced, short RNAs that repress and thus regulate the expression of almost half of known protein-coding genes. miRNA-mediated gene repression is an important regulatory mechanism to modulate fundamental cellular processes such as the cell cycle, growth, proliferation, phenotype, and death, which in turn have major influences on pathophysiological outcomes. In kidneys, miRNAs are indispensable for renal development and homeostasis. Emerging evidence has further pinpointed the pathogenic roles played by miRNAs in major renal diseases, including diabetic nephropathy, acute kidney injury, renal carcinoma, polycystic kidney disease, and others. Although the field of renal miRNA research is still in its infancy and important questions remain, future investigation on miRNA regulation in kidneys has the potential to revolutionize both the diagnosis and treatment of major renal diseases.

Fig. 1.

Biogenesis and function of microRNAs (miRNA). Most of miRNA genes are transcribed via RNA polymerase II, leading to the generation of pri-miRNAs that are long transcripts with multiple hairpin loop structures. Pri-miRNAs are processed by the Microprocessor protein complex containing Drosha, resulting in the generation of smaller precursor molecules called pre-miRNAs. pre-miRNAs are then exported from the nucleus via exportin-5. In the cytoplasm, the pre-miRNAs are further processed via Dicer to generate short, double-stranded miRNAs, which are then converted to mature, single-stranded miRNAs via RISC, a protein complex containing argonaute (AGO). Finally, mature miRNAs direct RISC to target gene mRNA, resulting in mRNA degradation (miRNA finds perfect complementary sequences in mRNA) or translational repression (imperfect complementary sequences in mRNA).

Fig. 2.

General scheme to study miRNA regulation of renal pathophysiology. The research can be divided into 3 phases to identify the miRNAs, determine their targets, and delineate their pathophysiological roles. A flow chart is presented to depict the relevant studies.