Cnidarian microRNAs frequently regulate targets by cleavage

In bilaterians, which comprise most of extant animals, microRNAs (miRNAs) regulate the majority of messenger RNAs (mRNAs) via base-pairing of a short sequence (the miRNA “seed”) to the target, subsequently promoting translational inhibition and transcript instability. In plants, many miRNAs guide endonucleolytic cleavage of highly complementary targets. Because little is known about miRNA function in nonbilaterian animals, we investigated the repertoire and biological activity of miRNAs in the sea anemone Nematostellavectensis, a representative of Cnidaria, the sister phylumof Bilateria. Our work uncovers scores of novel miRNAs in Nematostella, increasing the total miRNA gene count to 87. Yet only a handful are conserved in corals and hydras, suggesting that microRNA gene turnover in Cnidariagreatly exceeds that of other metazoan groups. We further show that NematostellamiRNAs frequently direct the cleavage of their mRNA targets via nearly perfect complementarity. This modeof actionresembles that of small interfering RNAs (siRNAs) and plant miRNAs. It appears to be common in Cnidaria, as several of the miRNA target sites are conserved among distantly related anemonespecies, and we also detected miRNA-directed cleavage in Hydra. Unlike in bilaterians, NematostellamiRNAs are commonly coexpressed with their target transcripts. In light of these findings, we propose that post-transcriptional regulationby miRNAs functions differently in Cnidariaand Bilateria. The similar, siRNA-like modeof actionof miRNAs in Cnidariaand plants suggests that this may be an ancestral state.