The study investigates the role of microRNA 122 (miR-122) in regulating hepatitis C virus (HCV) RNA abundance. MiR-122 is specifically expressed in the human liver and is highly abundant. The researchers found that sequestering miR-122 in liver cells results in a significant loss of autonomously replicating HCV RNAs. Genetic interactions between miR-122 and the 5' noncoding region (NCR) of the viral genome were revealed through mutational analyses and ectopic expression of miR-122 molecules with compensatory mutations. Replication-defective RNAs showed that miR-122 does not affect mRNA translation or RNA stability, suggesting that it facilitates viral RNA replication. The study concludes that miR-122 may be a potential target for antiviral intervention against HCV.The study investigates the role of microRNA 122 (miR-122) in regulating hepatitis C virus (HCV) RNA abundance. MiR-122 is specifically expressed in the human liver and is highly abundant. The researchers found that sequestering miR-122 in liver cells results in a significant loss of autonomously replicating HCV RNAs. Genetic interactions between miR-122 and the 5' noncoding region (NCR) of the viral genome were revealed through mutational analyses and ectopic expression of miR-122 molecules with compensatory mutations. Replication-defective RNAs showed that miR-122 does not affect mRNA translation or RNA stability, suggesting that it facilitates viral RNA replication. The study concludes that miR-122 may be a potential target for antiviral intervention against HCV.