Glucose stress causes mRNA retention in nuclear Nab2 condensates

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 to control gene expression during stress.通过核孔复合物（nuclear pore complexes）介导的核mRNA转运，是真核生物基因表达的核心步骤。尽管学界已对参与mRNA转运的诸多因子完成功能表征，但目前仍缺乏对该过程及其调控机制的系统性深入理解。本研究借助酵母单RNA成像（single-RNA imaging）技术，揭示了细胞在应激状态下通过mRNA滞留调控mRNA转运的机制。我们证实，当葡萄糖被撤除时，必需RNA结合因子Nab2会在细胞核内形成依赖于RNA的凝聚体样结构；该现象与核孔处DEAD-box ATP酶（DEAD-box ATPase）Dbp5的丰度降低同步发生。敲低Dbp5进而阻断mRNA转运，是诱导Nab2发生凝聚的充分且必要条件。Nab2的凝聚状态会影响核内mRNA的积累程度，且该现象可在体外实验中重现：此时Nab2可形成依赖于RNA的液态液滴。据此我们提出假说：细胞可通过凝聚过程在应激状态下调控mRNA转运，进而实现基因表达的精准调控。