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Unexpected Role of the Steroid-Deficiency Protein Ecdysoneless in Pre-mRNA Splicing


Steroid hormones perform pivotal roles in animal development, sexual maturation, reproduction, and physiology. Also insects possess a hormonal steroid, commonly known as ecdysone, that was originally found to promote ecdyses in growing larvae and their metamorphosis to adults. Since the discovery of ecdysone-inducible puffs on the polytene chromosomes in the 1960's, genetics of the Drosophila fruit flies has substantially advanced our understanding of steroid hormone impact on gene regulation during development. In the present study, we have solved an old puzzle of the “ecdysoneless” mutant that has traditionally provided investigators with a steroid-deficient animal model. Unexpectedly, we find that the Ecdysoneless protein (Ecd) does not primarily regulate ecdysone biosynthesis but that a critical steroidogenic enzyme requires Ecd for splicing of its precursor mRNA (pre-mRNA). Ecd physically contacts the immensely complex pre-mRNA splicing machinery. Outside the ecdysone-producing gland, Ecd is essential for survival of dividing cells within developing tissues. 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.


Vyšlo v časopise: Unexpected Role of the Steroid-Deficiency Protein Ecdysoneless in Pre-mRNA Splicing. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004287
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004287

Souhrn

Steroid hormones perform pivotal roles in animal development, sexual maturation, reproduction, and physiology. Also insects possess a hormonal steroid, commonly known as ecdysone, that was originally found to promote ecdyses in growing larvae and their metamorphosis to adults. Since the discovery of ecdysone-inducible puffs on the polytene chromosomes in the 1960's, genetics of the Drosophila fruit flies has substantially advanced our understanding of steroid hormone impact on gene regulation during development. In the present study, we have solved an old puzzle of the “ecdysoneless” mutant that has traditionally provided investigators with a steroid-deficient animal model. Unexpectedly, we find that the Ecdysoneless protein (Ecd) does not primarily regulate ecdysone biosynthesis but that a critical steroidogenic enzyme requires Ecd for splicing of its precursor mRNA (pre-mRNA). Ecd physically contacts the immensely complex pre-mRNA splicing machinery. Outside the ecdysone-producing gland, Ecd is essential for survival of dividing cells within developing tissues. 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.


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