CONICET | Buscador de Institutos y Recursos Humanos

Background: Trace elements regulate the expression of proteins related to their transport/metabolism by interacting with proteins bound to mRNA untranslated regions (UTR). We have demonstrated that iodide rapidly reduces NIS mRNA expression and poly(A) tail, leading to a reduced transcript half-life. Objective: Investigate if NIS mRNA 3UTR is responsive to iodide and responsible for the reduced stability of this transcript. Methods: PCCl3 cells were permanently transfected with peGFP-C2 plasmid containing or not the NIS mRNA 3UTR (eGFP-3UTR and eGFP cells). Both types of cells were divided into iodide and control groups, which were treated or not with NaI (10-3 M) for 30 min to 48 h. NIS and eGFP mRNA/protein expression were evaluated by Real-Time PCR/Western Blotting. NIS and eGFP mRNA half-lives were evaluated, by qPCR, in cells treated with actinomycin D (5 uM) for 1 h, and then, treated or not with NaI for 0 to 6 h. Results: Iodide treatment reduced the eGFP expression in eGFP-3UTR cells, but not in eGFP cells, in all periods of times studied. eGFP mRNA half-life was shorter in the eGFP-3UTR cells treated with iodide vs iodide-treated eGFP cells. Both types of cells presented reduced NIS expression and mRNA half-life after iodide treatment, confirming the treatment effectiveness. Conclusions: The iodide excess reduced eGFP transcript expression, half-life and eGFP protein expression in cells transfected with NIS mRNA 3UTR. This effect was not observed in eGFP cells, suggesting that NIS mRNA untranslated region presents at least one sequence of bases that is responsive to iodide, which, in excess, is capable to reduce the stability and the expression of the transcript. These data provide a new insight about the mechanism by which iodide regulates NIS expression at post-transcriptional level.