Mechanisms of miRNA-Mediated Gene Regulation from Common Downregulation to mRNA-Specific Upregulation

Figure 3

Activation of hepatitis C virus (HCV) expression by miR-122, a liver-specific microRNA. The mature single-stranded miR-122 is processed from its double- stranded precursor and incorporated into functional miRNP, bearing AGO2. miRNPs target one or two tandem binding sites in the 5′ noncoding region (5′NCR) of HCV RNA. HCV appears to usurp the miRNP to increase its RNA accumulation by a number of mechanisms. (a) First, miR-122 complexes provide a scaffold for the binding of essential factors such polymerase for RNA replication. (b) In addition, miRNP complexes increase the association of 40s ribosome subunit, and thus, result in increased translation and protein yield. (c) They also form an unusual oligomeric complex in 5′ end of HCV RNA and result in HCV RNA stability enhancement by masking its single-stranded 5′end through hiding 5′NCR from 5′ cytoplasmic exonucleases and immune sensors. (d) Also, miR-122 binding was reported to lead to increased propagation and life cycle of virus by some ill-defined mechanisms.