Abstract:
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.
摘要:
通过核孔复合物输出核mRNA是真核基因表达的重要步骤。尽管参与mRNA转运的因素已经被表征,缺乏对这一过程及其调控的全面机械理解。这里,我们在酵母中使用单RNA成像显示细胞在应激期间利用mRNA滞留来控制mRNA的输出.我们证明,葡萄糖戒断后,必需的RNA结合因子Nab2在细胞核中形成依赖RNA的缩合样结构。这与核孔处DEAD-boxATPaseDbp5的丰度降低相吻合。消耗Dbp5,从而阻断mRNA输出,是必要的,足以触发Nab2冷凝。Nab2缩合状态影响核mRNA积累的程度,可以在体外概括,其中Nab2形成依赖RNA的液滴。我们假设细胞在应激期间使用凝聚来调节mRNA输出和控制基因表达。