Specific inhibition of rRNA transcription and dynamic relocation of fibrillarin induced by mercury

Current evidence suggests that the nucleolus is composed of different subst ructures that are dynamic and form in response to the requirement for new r ibosome synthesis. Thus, agents that disrupt nucleolar organization may der egulate basic cellular events and eventually contribute to human disease, H ere we report that environmentally relevant concentrations (5 mu M) of inor ganic 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 transcriptio n assays: mercuric ions specifically blocked synthesis of ribosomal RNA, wh ereas activity of RNA polymerase II remained unchanged and occurred through out the nucleoplasm. Moreover, we show by double-labeling that inhibition o f nucleolar transcription and redistribution of fibrillarin occur simultane ously, underlining that fibrillarin relocation is a consequence of the bloc kade of bosomal RNA synthesis by mercury. We also detected redistribution o f fibrillarin in vivo, e.g., in splenic cells of mice chronically exposed t o HgCl2,, Thus, implications of this alteration of nuclear structure and fu nction for mercury-induced autoimmunity are discussed. (C) 2000 Academic Pr ess.