MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by binding to messenger RNAs (mRNAs). MiR-122 is a liver-specific miRNA that is highly abundant in the human liver. This study shows that miR-122 sequesters in liver cells and reduces the abundance of autonomously replicating hepatitis C virus (HCV) RNAs. The interaction between miR-122 and the 5' noncoding region (NCR) of the HCV genome was confirmed through mutational analyses and ectopic expression experiments. These findings suggest that miR-122 may facilitate HCV RNA replication and could be a potential target for antiviral therapy. MiR-122 is specifically expressed in the liver and constitutes about 70% of the total miRNA population. The study examined the role of miR-122 in regulating HCV gene expression by monitoring its expression in liver tissue and liver cell lines. MiR-122 was detected in mouse and human liver, as well as in cultured human Huh7 and mouse Hepa 1-6 liver cells, but not in human cervical carcinoma-derived HeLa cells. The study identified two predicted binding sites for miR-122 in the HCV genome, one in the 3' NCR and one in the 5' NCR. To determine whether miR-122 regulates HCV gene expression, the researchers tested whether its inactivation would alter the abundance of an autonomously replicating, dicistronic HCV RNA replicon. They found that inactivating miR-122 significantly reduced the abundance of HCV RNA and protein. The study also showed that miR-122 is required to maintain the abundance of both genotypes 1a and 1b RNA in stable cell lines and upon direct transfection of minimally modified genomic RNA. The study further investigated whether the putative miR-122 binding sites are required for the miR-122 effects on RNA abundance. They introduced mutations into the H77c cDNA and found that mutations in the 5' NCR seed match sequence significantly reduced RNA accumulation. However, mutations in the 3' NCR seed match sequence did not affect RNA accumulation. These findings suggest that the 5' NCR is critical for miR-122 effects on RNA abundance. The study also showed that miR-122 is required for the maintenance of HCV RNA and that its absence leads to reduced viral RNA accumulation. The researchers concluded that miR-122 may aid in RNA folding or RNA sequestration in replication complexes. The study also raises the question of whether 5' NCRs in other viral or host cell mRNAs can be targeted by microRNAs and whether such interactions regulate mRNAMicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by binding to messenger RNAs (mRNAs). MiR-122 is a liver-specific miRNA that is highly abundant in the human liver. This study shows that miR-122 sequesters in liver cells and reduces the abundance of autonomously replicating hepatitis C virus (HCV) RNAs. The interaction between miR-122 and the 5' noncoding region (NCR) of the HCV genome was confirmed through mutational analyses and ectopic expression experiments. These findings suggest that miR-122 may facilitate HCV RNA replication and could be a potential target for antiviral therapy. MiR-122 is specifically expressed in the liver and constitutes about 70% of the total miRNA population. The study examined the role of miR-122 in regulating HCV gene expression by monitoring its expression in liver tissue and liver cell lines. MiR-122 was detected in mouse and human liver, as well as in cultured human Huh7 and mouse Hepa 1-6 liver cells, but not in human cervical carcinoma-derived HeLa cells. The study identified two predicted binding sites for miR-122 in the HCV genome, one in the 3' NCR and one in the 5' NCR. To determine whether miR-122 regulates HCV gene expression, the researchers tested whether its inactivation would alter the abundance of an autonomously replicating, dicistronic HCV RNA replicon. They found that inactivating miR-122 significantly reduced the abundance of HCV RNA and protein. The study also showed that miR-122 is required to maintain the abundance of both genotypes 1a and 1b RNA in stable cell lines and upon direct transfection of minimally modified genomic RNA. The study further investigated whether the putative miR-122 binding sites are required for the miR-122 effects on RNA abundance. They introduced mutations into the H77c cDNA and found that mutations in the 5' NCR seed match sequence significantly reduced RNA accumulation. However, mutations in the 3' NCR seed match sequence did not affect RNA accumulation. These findings suggest that the 5' NCR is critical for miR-122 effects on RNA abundance. The study also showed that miR-122 is required for the maintenance of HCV RNA and that its absence leads to reduced viral RNA accumulation. The researchers concluded that miR-122 may aid in RNA folding or RNA sequestration in replication complexes. The study also raises the question of whether 5' NCRs in other viral or host cell mRNAs can be targeted by microRNAs and whether such interactions regulate mRNA