Griffis Eric R, Craige Branch, Dimaano Christian, Ullman Katharine S, Powers Maureen A
Emory University School of Medicine, Department of Cell Biology, Atlanta, Georgia 30322-1100, USA.
Mol Biol Cell. 2004 Apr;15(4):1991-2002. doi: 10.1091/mbc.e03-10-0743. Epub 2004 Jan 12.
Despite the apparent overall structural stability of the nuclear pore complex during interphase, at least two nucleoporins have been shown to move dynamically on and off the pore. It is not yet certain what contribution nucleoporin mobility makes to the process of nuclear transport or how such mobility is regulated. Previously, we showed that Nup98 dynamically interacts with the NPC as well as bodies within the nucleus in a transcription-dependent manner. We have extended our studies of dynamics to include Nup153, another mobile nucleoporin implicated in RNA export. In both cases, we found that although only one domain is essential for NPC localization, other regions of the protein significantly affect the stability of association with the pore. Interestingly, like Nup98, the exchange of Nup153 on and off the pore is inhibited when transcription by Pol I and Pol II is blocked. We have mapped the regions required to link Nup98 and Nup153 mobility to transcription and found that the requirements differ depending on which polymerases are inhibited. Our data support a model whereby transcription of RNA is coupled to nucleoporin mobility, perhaps ultimately linking transport of RNAs to a cycle of remodeling at the nuclear pore basket.
尽管核孔复合体在间期表面上具有整体结构稳定性,但至少有两种核孔蛋白已被证明可在核孔上动态进出。目前尚不确定核孔蛋白的流动性对核运输过程有何贡献,以及这种流动性是如何被调控的。此前,我们发现Nup98以转录依赖的方式与核孔复合体以及细胞核内的结构动态相互作用。我们将动力学研究扩展到另一种与RNA输出有关的可移动核孔蛋白Nup153。在这两种情况下,我们发现虽然只有一个结构域对于核孔复合体定位至关重要,但蛋白质的其他区域会显著影响与核孔结合的稳定性。有趣的是,与Nup98一样,当RNA聚合酶I和RNA聚合酶II的转录被阻断时,Nup153在核孔上的进出交换也会受到抑制。我们已经确定了将Nup98和Nup153的流动性与转录联系起来所需的区域,并且发现根据所抑制的聚合酶不同,要求也有所不同。我们的数据支持一种模型,即RNA转录与核孔蛋白的流动性相偶联,这可能最终将RNA的运输与核孔篮处的重塑循环联系起来。