Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland.
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland; Biozentrum, Center for Molecular Life Sciences, University of Basel, 4056 Basel, Switzerland.
Cell Rep. 2024 Jan 23;43(1):113593. doi: 10.1016/j.celrep.2023.113593. Epub 2023 Dec 18.
Nuclear mRNA export via nuclear pore complexes is an essential step in eukaryotic gene expression. Although factors involved in mRNA transport have been characterized, a comprehensive mechanistic understanding of this process and its regulation is lacking. Here, we use single-RNA imaging in yeast to show that cells use mRNA retention to control mRNA export during stress. We demonstrate that, upon glucose withdrawal, the essential RNA-binding factor Nab2 forms RNA-dependent condensate-like structures in the nucleus. This coincides with a reduced abundance of the DEAD-box ATPase Dbp5 at the nuclear pore. Depleting Dbp5, and consequently blocking mRNA export, is necessary and sufficient to trigger Nab2 condensation. The state of Nab2 condensation influences the extent of nuclear mRNA accumulation and can be recapitulated in vitro, where Nab2 forms RNA-dependent liquid droplets. We hypothesize that cells use condensation to regulate mRNA export and control gene expression during stress.
核 mRNA 通过核孔复合体的输出是真核基因表达的一个基本步骤。尽管已经鉴定了参与 mRNA 运输的因子，但对这个过程及其调控的全面机制理解还很缺乏。在这里，我们使用酵母中的单 RNA 成像显示，细胞在应激期间使用 mRNA 保留来控制 mRNA 输出。我们证明，在葡萄糖耗尽后，必需的 RNA 结合因子 Nab2 在核内形成依赖于 RNA 的凝结物样结构。这与 DEAD -box ATP 酶 Dbp5 在核孔处的丰度降低相一致。耗尽 Dbp5，并因此阻断 mRNA 输出，是触发 Nab2 凝结所必需且充分的条件。Nab2 凝结的状态影响核内 mRNA 积累的程度，并且可以在体外重现，其中 Nab2 形成依赖于 RNA 的液滴。我们假设细胞使用凝结来调节 mRNA 输出，并在应激期间控制基因表达。
