miRNAs (microRNAs) are important regulators of gene expression. In higher eukaryotes, the tightly controlled expression of different miRNAs, each of which regulates multiple target mRNAs, is crucial for the maintenance of tissue type and the control of differentiation. miR - 122 is a highly liver-specific miRNA that is important in hepatitis C virus infection, cholesterol metabolism and hepatocellular carcinoma. In the present review, we discuss the effects of miR - 122 on liver physiology and pathology. Recent evidence of pathways involved in the regulation of miR - 122 expression is also considered.
Most metazoan miRNAs (microRNAs) bind to sites in the 3′-UTRs (untranslated regions) of mRNA targets and negatively regulate protein synthesis. The liver-specific miR - 122 , however, exerts a positive effect on HCV (hepatitis C virus) RNA levels by binding directly to a site in the 5′-UTR of the viral RNA. HCV translation and RNA stability are unaffected, and therefore miR - 122 is likely to act at the level of viral replication. The miR - 122 -binding site in HCV RNA was examined to determine whether the nature of the site is responsible for the unusual mode of action for a miRNA. When the site was placed in the 3′-UTR of a reporter mRNA, miR - 122 repressed translation, and therefore the location of the miR - 122 -binding site dictates its effect on gene expression. Additionally, a second binding site for miR - 122 was identified in the HCV 5′-UTR, and miR - 122 binding to both sites in the same viral RNA was found to be necessary for viral replication. The two sites are adjacent and are separated by a short spacer, which is largely conserved between HCV genotypes. The binding site requirements for miR - 122 to positively regulate HCV replication provide an insight into this unusual mode of miRNA action.