Dear Editor,A current major challenge in microRNA (miRNA) biology is the elucidation of their functions.A key first step in this pursuit is the identification of functionally relevant miRNA:target gene relationships.Although the molecular verification of miRNA targets with degradome or 5-end RACE approaches has been very successful in plants,the detection of miRNAguided cleavage products may not be reflective of functional importance (Allen et al.,2010),which can only be definitively defined by genetic approaches.This remains challenging,as isolation of loss-of-function mutations in miRNA genes has been rare,due to both their small size and the fact that many exist in multi-gene families.Consequently,much of our current understanding of miRNA function has relied heavily on gain-of-function approaches,such as the transgenic expression of miRNA-resistant target genes,where multiple synonymous mutations are created within the miRNA binding site of a putative target gene,conferring the gene resistant to miRNA regulation (Garcia,2008).By comparing the phenotypic impact of the expression of this miRNA-resistant target to its wild-type counterpart,functionally significant miRNAmediated regulation may be elucidated.