Specific inhibition of rRNA transcription and dynamic relocation of fibrillarin induced by mercury
Specific inhibition of rRNA transcription and dynamic relocation of fibrillarin induced by mercury
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DOI：
10.1006/excr.2000.4923
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发表时间：
2000-08-25
影响因子：
3.7
通讯作者：
von Mikecz, A
中科院分区：
文献类型：
--
作者：
Chen, M;von Mikecz, A
目前的证据表明，核仁由不同的亚结构组成，这些亚结构是动态的，并根据新核糖体合成的需要而形成。因此，破坏核仁组织的药物可能会解除对基本细胞事件的调节，并最终导致人类疾病。在这里，我们报告了环境相关浓度（5 μ M）的无机汞诱导核仁蛋白纤原蛋白从核仁重新分布到上皮细胞系的核质中。由于使用转录抑制剂治疗会导致类似的纤原蛋白重新定位，因此通过连续转录试验研究了汞对转录的影响：汞离子特异性地阻断核糖体RNA的合成，而RNA聚合酶II的活性保持不变，并在整个核质中发生。此外，我们通过双标记表明，核仁转录的抑制和纤原蛋白的重新分配同时发生，强调纤原蛋白的重新定位是汞阻断核糖核酸合成的结果。我们还在体内检测到纤原蛋白的重新分布，例如在长期暴露于HgCl2的小鼠的脾细胞中，因此，我们讨论了这种核结构和功能改变对汞诱导的自身免疫的影响。(C) 2000年学术出版社。
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 mu M) 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 bosomal 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. (C) 2000 Academic Press.