Dyskerin localizes to the mitotic apparatus and is required for orderly mitosis in human cells.
Dyskerin localizes to the mitotic apparatus and is required for orderly mitosis in human cells.
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DOI：
10.1371/journal.pone.0080805
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lin P
中科院分区：
文献类型：
--
作者：
Alawi F;Lin P
Dyskerin是一种高度保守的核仁RNA结合蛋白，在小核核糖核蛋白生物发生、端粒酶和端粒维持以及前体rRNA加工中发挥着既定作用。端粒酶在S期有功能，大部分rRNA成熟发生在G1和S期;这两个过程在有丝分裂期间失活。然而，我们表明，在细胞周期进程的过程中，人dyskerin表达高峰期在G2/M与促有丝分裂因子的上调平行。在前中期、中期和后期，Dyskerin从间期细胞的核仁重新分布到染色体周区。随着后期进程的继续，dyskerin也定位于中极区的细胞质中。通过siRNA介导的dyskerin功能的缺失促进了G2/M积累，这伴随着有丝分裂指数的增加和纺锤体组装检查点的激活。活细胞成像进一步揭示了一系列有丝分裂缺陷，包括前中期进展延迟、多极纺锤体发生率显著增加以及最终导致微核形成的后期桥。总之，这些发现表明，dyskerin是一种在整个细胞周期中高度动态的蛋白质，并增加了因其正常功能缺失而被破坏的基本细胞过程的全部功能。
Dyskerin is a highly conserved, nucleolar RNA-binding protein with established roles in small nuclear ribonucleoprotein biogenesis, telomerase and telomere maintenance and precursor rRNA processing. Telomerase is functional during S phase and the bulk of rRNA maturation occurs during G1 and S phases; both processes are inactivated during mitosis. Yet, we show that during the course of cell cycle progression, human dyskerin expression peaks during G2/M in parallel with the upregulation of pro-mitotic factors. Dyskerin redistributed from the nucleolus in interphase cells to the perichromosomal region during prometaphase, metaphase and anaphase. With continued anaphase progression, dyskerin also localized to the cytoplasm within the mid-pole region. Loss of dyskerin function via siRNA-mediated depletion promoted G2/M accumulation and this was accompanied by an increased mitotic index and activation of the spindle assembly checkpoint. Live cell imaging further revealed an array of mitotic defects including delayed prometaphase progression, a significantly increased incidence of multi-polar spindles, and anaphase bridges culminating in micronucleus formation. Together, these findings suggest that dyskerin is a highly dynamic protein throughout the cell cycle and increases the repertoire of fundamental cellular processes that are disrupted by absence of its normal function.
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