Specific Inhibition of rRNA Transcription and Dynamic Relocation of Fibrillarin Induced by Mercury

Abstract

Current evidence suggests that the nucleolus is composed of different substructures that are dynamic and form in response to the requirement for new ribosome synthesis. Thus, agents that disrupt nucleolar organization may deregulate basic cellular events and eventually contribute to human disease. Here we report that environmentally relevant concentrations (5 μM) of inorganic mercury induce a redistribution of nucleolar protein fibrillarin from the nucleolus to the nucleoplasm in epithelial cell lines. Since treatment with transcription inhibitors led to a similar relocation of fibrillarin, the effects of mercury on transcription were studied by run-on transcription assays: mercuric ions specifically blocked synthesis of ribosomal RNA, whereas activity of RNA polymerase II remained unchanged and occurred throughout the nucleoplasm. Moreover, we show by double-labeling that inhibition of nucleolar transcription and redistribution of fibrillarin occur simultaneously, underlining that fibrillarin relocation is a consequence of the blockade of ribosomal RNA synthesis by mercury. We also detected redistribution of fibrillarin in vivo, e.g., in splenic cells of mice chronically exposed to HgCl2. Thus, implications of this alteration of nuclear structure and function for mercury-induced autoimmunity are discussed.