Micro RNAs (miRNAs) are a recently discovered class of small, non-coding RNAs with the function of post-transcriptional gene expression regulation. MiRNAs may function in networks, forming a complex relationship with diseases. Alterations of specific miRNA levels have significant correlation with diseases of divergent origin, such as diabetic or ischemic organ injury including nephropathy, and malignant diseases including renal tumors. After identification of disease-associated miRNAs, there are two options of influencing their tissue expression. The function of miRNAs can be inhibited by antisense oligonucleotides (ASOs), which have been shown to silence specific miRNAs in vivo. Moreover, miRNA activity can be also mimicked or enhanced by delivering chemically synthesized miRNAs. Thus, modifying the expression of miRNAs is a potential future gene-therapeutic tool to influence posttranscriptional regulation of multiple genes in a single therapy. In this review we focus on key renal miRNAs with the aim of revealing the pathomechanisms of renal diseases. Nucleic acid therapy with oligonucleotides and short interfering RNA (siRNA) are under clinical evaluation presently. Similar therapeutic strategies, to influence miRNA function is also already under clinical investigation in RNA interference trials. We summarize here studies specifically aimed at the modification of miRNA expression. Research on the post-transcriptional regulation of gene expression by miRNA may reshape our understanding of renal pathophysiology and consequently may bring new diagnostic markers and therapeutic agents.
The translation of mRNA can also be controlled by a number of mechanisms, mostly at the level of initiation. Recruitment of the small ribosomal subunit can indeed be modulated by mRNA secondary structure, antisense RNA binding, or protein binding. In both prokaryotes and eukaryotes, a large number of RNA binding proteins exist, which often are directed to their target sequence by the secondary structure of the transcript, which may change depending on certain conditions, such as temperature or presence of a ligand (aptamer). Some transcripts act as ribozymes and self-regulate their expression.