microRNAs are currently believed to control a large diversity of physiologic processes, through the collective repression of thousands of target genes. Both experimental and computational analyses indeed suggest that each microRNA regulates tens or hundreds of genes. But some observations suggest that the phenotypic consequences of many published miRNA/mRNA interactions are dubious. For example, the reported amplitude of miRNA-guided repression is very small, while biologic processes tend to be robust to small changes in gene expression. We recently showed, on one particular miRNA, that for most predicted targets, miRNA-guided repression is even smaller than inter-individual variability among wild-type specimens. We also put forward several sources of computational false positives. These issues are generally neglected by the scientific community, probably resulting in the frequent publication of irreproducible or misinterpreted results regarding microRNA function. We propose novel types of analyses, easily accessible to the community, that could help improve microRNA target identification.
Keywords: False positives; inter-individual variability; microRNA; over-conservation; robustness; target identification.