Friday, March 20, 2015

Role of microRNA in liver function and HCV infection

A recent study published in Cell details how microRNA-122 interacts with both human liver cells and hepatitis C virus. Normally, liver cells use miRNA-122 to turn down gene expression by guiding several silencing proteins to various RNA transcripts. In this way, miRNA-122 helps control cholesterol and iron metabolism, circadian rhythms, and other normal liver cell functions. Though miRNA-122 serves several important cellular functions, it also plays a substantial role in persistent HCV infection. In order to establish persistence, HCV binds to miRNA-122 to stabilize and protect the virus during its replication cycle.

Using a technique called cross-linking and immunoprecipitation (CLIP), the researchers identified interactions between miRNA-122 and Argonaute, one of the proteins involved in gene silencing. They found much lower levels of miRNA-122 activity in infected liver cells compared to uninfected liver cells, which means genes that would normally get silenced remain active. The authors postulate that HCV "sops up" miRNA-122 to cause live dysfunction, an idea that provides a molecular link between HCV infection and its associated pathologies: low levels of miRNA-122 activity over a long period of time may contribute to liver damage and even liver cancer, both of which have been associated with chronic HCV infection.

- Nick

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