Both have to cope with fluctuations in osmotic pressure and acidity. Flynt et al. now show how a microRNA (miRNA) molecule acts as a crucial part of the osmoregulatory machinery.
miRNAs are small noncoding RNAs that bind to gene transcripts, preventing their translation into proteins. There are potentially thousands of miRNAs encoded in the genomes of higher eukaryotes, and predicting their target transcripts is tricky, as binding occurs via imperfect sequence matches.
Researchers like Flynt and colleagues are taking a one-at-a-time approach to identify miRNA targets and functions, starting with the most highly conserved miRNAs. Among these are the miR-8 family, which has several conserved members in vertebrates. In fish, the team observed, miR-8 family members were abundant in cells called ionocytes. These cells are dotted throughout the skin and participate in osmoregulation.
Without miR-8, ionocytes looked normal, but couldn't cope with pH changes or osmotic stress—in the latter case the fish developed edemas due to water retention. miR-8, it turns out, was targeting an mRNA that encodes a protein called nherf1 (Na+/H+ exchange regulatory factor 1). Originally identified in renal brush border membrane extracts, Nherf1 acts as an adaptor between the plasma membrane and cytoskeleton. In ionocytes lacking miR-8 family members, membrane trafficking of ion channels and other proteins was disrupted.
miR-8 is predicted to target nherf1 in mammals too. The team now plans to see whether intercalated cells of the kidney—the functional equivalents to ionocytes—use the same osmotic regulation pathway.
