It is now realized that mammalian cells can produce more than 200 different forms of what are referred to as microRNAs.These are small 21-26 nucleotide RNA species,that can function to negatively regulate the translation or stability of specific mRNA species.The present study is concerned with miR-122,a liver-specific microRNA.Some years ago Buendia and colleagues characterized a liver tumor in which a gene,which they called hcr,was translocated to c-myc,thereby profoundly activating c-myc expression.Later,Tuschl and colleagues showed that miR-122,the most abundant microRNA in the mammalian liver,was derived by RNA-processing of mRNA transcripts of this same hcr gene.We have found that liver-specific accumulation of miR-122 begins during embryonic development.At the same time,the levels of a predicted target for miR-122 action undergo a corresponding liver-specific decrease.The mRNA for this target,CAT-1,a cationic amino acid transporter,is predicted to contain at least 6 target sites for miR-122 action.We have used a reporter assay to show that three of these target sites are sufficient to render a gene susceptible to miR-122 action.Our miR-122 studies contribute to what will ultimately be many searches of the origin and function(s) of mammalian microRNA species.