Cnidarian microRNAs shed new light on the evolution of post-transcriptional regulation

Over the last decade microRNAs (miRNAs) have been shown to play pivotal roles as post-transcriptional regulators of gene expression in plants and animals. MiRNAs can be found in a wide range of animals, yet their functions were studied almost exclusively in bilaterian animals. Thus, studying their function in non-bilaterian phyla such as Cnidaria is crucial for understanding the evolution of miRNAs in early animals. Our previous results indicated that cnidarian miRNAs frequently have a nearly perfect match to their messenger RNA targets, resulting in target cleavage (slicing). Perfect binding of a miRNA to its target also leads to the degradation of the small RNA, unless it is protected by a methyl group at its 3′ end. Indeed, we find that miRNAs are frequently methylated in Cnidaria and that their stability depends on the HEN1 methyltransferase. Loss of HEN1 results in a significant decrease in miRNA levels and defective development of the cnidarian model, the starlet sea anemone Nematostella vectensis. Interestingly, knockdowns of major miRNA biogenesis factors and effectors such as Dicer1 or the two members of the Argonaute (AGO) family, phenocopies the HEN1 knockdown. Thus, we conclude that like in both plants and bilaterian animals, cnidarian development depends on a functional miRNA pathway. Further, we reveal that the two AGO proteins of Nematostella carry vastly different small RNA cargos, including structurally distinct miRNAs and this specialization uncovers the evolutionary history of miRNAs in sea anemones and the way by which these regulatory RNAs are born in Cnidaria.