Eukaryotic pseudouridine synthases direct RNA pseudouridylation and bind H⁄ACA small nucleolar RNA (snoRNAs), which, in turn, may act as precursors of microRNA-like molecules. In humans, loss of pseudouridine synthase activity causes dyskeratosis congenita (DC), a complex systemic disorder characterized by cancer susceptibility, failures in ribosome biogen-esis and telomere stability, and defects in stem cell formation.