Mohajan Suman, Rubio Linda S, Gross David S
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
J Biol Chem. 2025 Sep;301(9):110568. doi: 10.1016/j.jbc.2025.110568. Epub 2025 Aug 6.
The nuclear pore complex (NPC), a multisubunit complex located within the nuclear envelope, regulates RNA export and the import and export of proteins. Here, we address the role of the NPC in driving thermal stress-induced 3D genome repositioning of heat shock-response (HSR) genes in budding yeast. We found that two nuclear basket proteins, Nup2 and Mlp1, although dispensable for NPC integrity, are required for driving HSR genes into coalesced chromatin clusters, consistent with their strong, heat shock-dependent recruitment to HSR gene regulatory and coding regions. HSR gene clustering occurs predominantly within the nucleoplasm and is independent of the essential scaffold-associated proteins Nup1 and Nup145. Notably, acute double depletion of Nup2 and Mlp1 has little effect on the formation of Heat shock factor 1-containing transcriptional condensates, Heat shock factor 1 and Pol II recruitment to HSR genes, or HSR mRNA abundance. Our results define a 3D genome restructuring role for nuclear basket proteins extrinsic to the NPC and downstream of HSR gene activation.
核孔复合体（NPC）是位于核膜内的多亚基复合体，负责调节RNA输出以及蛋白质的输入和输出。在此，我们探讨了NPC在驱动热应激诱导的芽殖酵母中热休克反应（HSR）基因的三维基因组重定位中的作用。我们发现，两种核篮蛋白Nup2和Mlp1，虽然对NPC的完整性并非必需，但对于将HSR基因驱动到凝聚的染色质簇中是必需的，这与它们在热休克依赖下强烈募集到HSR基因调控区和编码区一致。HSR基因聚类主要发生在核质内，并且独立于必需的支架相关蛋白Nup1和Nup145。值得注意的是，Nup2和Mlp1的急性双缺失对含热休克因子1的转录凝聚物的形成、热休克因子1和Pol II募集到HSR基因上，或HSR mRNA丰度几乎没有影响。我们的结果确定了核篮蛋白在NPC外部且在HSR基因激活下游的三维基因组重组作用。
