Projects > Splicing in development and disease

Drosophila conditional ecdysoneless (ecd) mutants are characterized by the low titer of the major insect steroid hormone ecdysone. Since its discovery in 1977, ecd mutants have been widely used to test effects of steroid hormone signaling on gene regulation, animal development, reproduction and physiology although the molecular function of Ecd remained unknown. We found that Ecd does not primarily regulate ecdysone biosynthesis but that a critical steroidogenic enzyme requires Ecd for splicing of its pre-mRNA. Ecd directly interacts with core components of the U5 snRNP spliceosomal complex, including the conserved Prp8 protein. Consistently with its role in pre-mRNA splicing, Ecd is cell-autonomously required for survival of proliferating epithelial cells within the imaginal discs. Despite vast evolutionary distance, a human homolog of Ecd can functionally substitute for its counterpart in the fly. A conserved role of Ecd in pre-mRNA splicing might underlie a recently described involvement of mammalian Ecd in cell cycle progression and its contribution to malignancy of certain tumor types (Claudius et al., 2014, PLOS Genetics).