Department of Cell Biology, University of Alberta, Edmonton, AB, Canada, T6G 2H7.
Department of Cell Biology, University of Alberta, Edmonton, AB, Canada, T6G 2H7
J Cell Sci. 2020 Mar 26;133(6):jcs237156. doi: 10.1242/jcs.237156.
Nuclear pore complexes (NPCs) control gene expression by regulating the bi-directional exchange of proteins and RNAs between nuclear and cytoplasmic compartments, including access of transcriptional regulators to the nucleoplasm. Here, we show that the yeast () nucleoporin Nup170, in addition to binding and silencing subtelomeric genes, supports transcription of genes regulated by the SAGA transcriptional activator complex. Specifically, we show that a lower amount of SAGA complex is bound to target genes in the absence of Nup170. Consistent with this observation, levels of the SAGA complex are decreased in cells lacking Nup170, while those of the SAGA-related SLIK complexes are increased. This change in the ratio of SAGA to SLIK complexes is due to increased nuclear activity of Pep4, a protease responsible for production of the SLIK complex. Further analyses of various nucleoporin mutants revealed that the increased nuclear entry of Pep4 observed in the Δ mutant likely occurs as the consequence of an increase in the sieving limits of the NPC diffusion channel. On the basis of these results, we propose that changes in passive diffusion rates represent a mechanism for regulating SAGA- and SLIK complex-mediated transcriptional events.
核孔复合物（NPC）通过调节蛋白质和 RNA 在核质和细胞质隔间之间的双向交换来控制基因表达，包括转录调节因子进入核质。在这里，我们表明，酵母（）核孔蛋白 Nup170 除了结合和沉默端粒基因外，还支持由 SAGA 转录激活复合物调节的基因的转录。具体而言，我们表明，在没有 Nup170 的情况下，靶基因结合的 SAGA 复合物数量减少。与这一观察结果一致，在缺乏 Nup170 的细胞中，SAGA 复合物的水平降低，而 SAGA 相关的 SLÍK 复合物的水平增加。SAGA 与 SLÍK 复合物比率的这种变化是由于负责 SLÍK 复合物产生的肽酶 Pep4 的核活性增加所致。对各种核孔蛋白突变体的进一步分析表明，在 Δ 突变体中观察到的 Pep4 核内进入增加可能是由于 NPC 扩散通道的筛分限制增加所致。基于这些结果，我们提出，被动扩散速率的变化代表了调节 SAGA 和 SLÍK 复合物介导的转录事件的一种机制。
