The biological functions of miRNAs: lessons from in vivo studies

•The activity of miRNAs is essential for animal development and viability.•Deletion of individual miRNAs often leads to subtle or no phenotypic consequences.•miRNAs can have high levels of redundancy and are often placed in regulatory loops.•miRNAs can buffer gene expression against internal and external perturbations.

Despite their clear importance as a class of regulatory molecules, pinpointing the relevance of individual miRNAs has been challenging. Studies querying miRNA functions by overexpressing or silencing specific miRNAs have yielded data that are often at odds with those collected from loss-of-functions models. In addition, knockout studies suggest that many conserved miRNAs are dispensable for animal development or viability. In this review, we discuss these observations in the context of our current knowledge of miRNA biology and review the evidence implicating miRNA-mediated gene regulation in the mechanisms that ensure biological robustness.