Target complementarity in cnidarians supports a common origin for animal and plant microRNAs

microRNAs (miRNAs) are important post-transcriptional regulators that activate silencing mechanisms by annealing to mRNA transcripts. While plant miRNAs match their targets with nearly-full complementarity leading to mRNA cleavage, miRNAs in most animals require only a short sequence called seed to inhibit target translation. Recent findings showed that miRNAs in cnidarians, early-branching metazoans, act similarly to plant miRNAs, by exhibiting full complementarity and target cleavage; however, it remained unknown if seed- based regulation was possible in cnidarians. Here, we investigate the miRNA-target complementarity requirements for miRNA activity in the cnidarian Nematostella vectensis. We show that bilaterian-like complementarity of seed-only or seed and supplementary 3 matches are insufficient for miRNA-mediated knockdown. Furthermore, miRNA-target mismatches in the cleavage site decrease knockdown efficiency. Finally, miRNA silencing of a target with three seed binding sites in the 3 untranslated region that mimics typical miRNA targeting was repressed in zebrafish but not in Nematostella and Hydractinia symbiolongicarpus. Altogether, these results unravel striking similarities between plant and cnidarian miRNAs consolidating the evidence for common evolutionary origin of miRNAs in plants and animals.