miR-122 is a miRNA that is conserved among vertebrate species. miR-122 is not present in invertebrates, and no close paralogs of miR-122 have been detected. miR-122 is highly expressed in the liver, where it has been implicated as a regulator of fatty-acid metabolism in mouse studies. Reduced miR-122 levels are associated with hepatocellular carcinoma. miR-122 also plays an important positive role in the regulation of hepatitis C virus replication. Expression and regulation miR-122 was originally identified by cloning of tissue-specific microRNAs in mouse, where its expression is restricted to the liver. The liver-specific expression of miR-122 is conserved in zebrafish. miR-122 expression increases during embryogenesis until it constitutes 72% of total miRNA in adult human liver, making it one of the most highly expressed miRNAs in any tissue. In humans, miR-122 is encoded at a single genomic locus in chromosome 18. The primary miR-122 transcript (pri-miR-122) is a long non-coding RNA. Transcription is regulated by HNF4α. The miR-122 hairpin precursor consensus shown here is predicted based on base pairing and cross-species conservation. The mature sequence is excised from the 5' arm of the hairpin. There is evidence that miR-122 is regulated by Rev-ErbA alpha which is involved in circadian gene expression, suggesting that miR-122 is a circadian metabolic regulator. miR-122 regulates the expression of several mRNA molecules that are important in the circadian cycle, such as PPARβ/δ. Mature miR-122 is subject to modification by the poly(A) polymerase GLD-2, which adds a single adenosine to the miRNA 3' end. This results in an increase in miR-122 stability. Targets miR-122 regulates the synthesis of the protein CAT-1 by binding to sites in the mRNA 3'UTR such that translation is repressed and the mRNA is targeted to P bodies. This repression can be relieved by the protein HuR, which is released from the nucleus under conditions of cell stress and binds to the CAT-1 3'UTR. The HuR interaction leads to release of the mRNA from the P bodies and resumption of active translation. A number of other miR-122 targets, including CD320, AldoA and BCKDK, have been identified by microarray analysis of changes in mRNA expression in the liver of mice treated with miR-122 inhibitors. The overall effect of miR-122 inhibition is to reduce the plasma cholesterol level, although the pathways involved in this regulation have not been fully elucidated. miR-122 also regulates systemic iron homeostasis via the target mRNAs Hjv and Hfe. miR-122