A pan-cnidarian microRNA is an ancient biogenesis regulator of stinging cells

An ancient evolutionary innovation of a novel cell-type, the stinging cell (cnidocyte), appeared >600 million years ago in the phylum Cnidaria (sea anemones, corals, hydroids, and jellyfish). A complex bursting nano-injector of venom, the cnidocyst, is embedded in cnidocytes and enables cnidarians paralyzing prey and predators, contributing to this phylum’s evolutionary success. In this work, we show that post-transcriptional regulation by a pan-cnidarian microRNA, miR-2022, is essential for biogenesis of these cells. By manipulation of miR-2022 levels in a transgenic reporter line of cnidocytes in the sea anemone Nematostella vectensis, followed by transcriptomics, single-cell data analysis, prey paralysis assays, and cell sorting of transgenic cnidocytes, we reveal that miR-2022 enables cnidocyte biogenesis, while exhibiting a conserved expression domain with its targets in cnidocytes of other cnidarian species. Thus, here we reveal one of nature’s most ancient microRNA-regulated processes by studying the functional basis for its conservation.