Alternative splicing of the nuclear progestin receptor in a perciform teleost generates novel mechanisms of dominant-negative transcriptional regulation

摘要: In mammals, downstream function of the nuclear progestin receptor (PGR) can be differentially regulated in each target tissue by altering expression levels PGR mRNA variants. Such isoforms have also been identified birds and reptiles, but not non-amniote vertebrates. Based upon extensive phylogenetic, syntenic functional analyses, here we show that higher orders Teleostei retain a single pgr gene, four different transcript variants extant gene are expressed ovary an evolutionary advanced perciform teleost, gilthead seabream (Sparus aurata). Three (pgr_tv2, pgr_tv3 pgr_tv4) arise from alternative pre-mRNA splicing resulting N-terminally truncated receptors, whereas one isoform (pgr_tv1) is deletion variant. Seabream wild-type Pgr shows highest transactivational response to native euteleostean progestins, 17α,20β-dihydroxy-4-pregnen-3-one 17α,20β,21-trihydroxy-4-pregnen-3-one, Pgr_tv3 Pgr_tv4 independently regulate novel cytosolic mechanisms dominant-negative repression Pgr-mediated transcription. ovary, protein localized oogonia, nuclei primary (previtellogenic) oocytes, as well follicular (granulosa) cells oocyte cytoplasm early late vitellogenic ovarian follicles. Expression pgr, pgr_tv4 was ovaries, while both inhibitory isoforms, decreased during vitellogenesis. Stimulation explants vitro with recombinant piscine follicle-stimulating hormone estrogen temporal pgr_tv4. These findings suggest that, responsiveness seabream, particularly oogenesis, may through mRNA. Thus, mechanism transcriptional regulation likely evolved prior separation Actinopterygii (ray-finned fishes) Sarcopterygii (lobe-finned fishes).