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Karyopherin Kap114p-mediated trans-repression controls ribosomal gene expression under saline stress.
EMBO Reports ( IF 6.5 ) Pub Date : 2020-06-02 , DOI: 10.15252/embr.201948324
Chung-Chi Liao,Sahana Shankar,Wen-Chieh Pi,Chih-Chia Chang,Golam Rizvee Ahmed,Wei-Yi Chen,Kuo-Chiang Hsia

Nuclear accessibility of transcription factors controls gene expression, co‐regulated by Ran‐dependent nuclear localization and a competitive regulatory network. Here, we reveal that nuclear import factor‐facilitated transcriptional repression attenuates ribosome biogenesis under chronic salt stress. Kap114p, one of the karyopherin‐βs (Kap‐βs) that mediates nuclear import of yeast TATA ‐binding protein (yTBP ), exhibits a yTBP ‐binding affinity four orders of magnitude greater than its counterparts and suppresses binding of yTBP with DNA . Our crystal structure of Kap114p reveals an extensively negatively charged concave surface, accounting for high‐affinity basic‐protein binding. KAP 114 knockout in yeast leads to a high‐salt growth defect, with transcriptomic analyses revealing that Kap114p modulates expression of genes associated with ribosomal biogenesis by suppressing yTBP binding to target promoters, a trans‐repression mechanism we attribute to reduced nuclear Ran levels under salinity stress. Our findings reveal that Ran integrates the nuclear transport pathway and transcription regulatory network, allowing yeast to respond to environmental stresses.

中文翻译:

在盐胁迫下,核转运蛋白Kap114p介导的反式调控控制核糖体基因表达。

转录因子的核可及性控制基因表达,由Ran依赖性核定位和竞争性调控网络共同调控。在这里,我们揭示了核输入因子促进的转录抑制减弱了慢性盐胁迫下核糖体的生物发生。Kap114p是介导酵母TATA结合蛋白(yTBP)核输入的核蛋白-βs(Kap-βs)之一,它的yTBP结合亲和力比对应的亲和力大4个数量级,并抑制yTBP与DNA的结合。我们的Kap114p晶体结构揭示了一个带大量负电荷的凹面,说明了高亲和力的碱性蛋白结合。KAP 114酵母中的敲除导致高盐生长缺陷,转录组学分析显示,Kap114p通过抑制yTBP与靶标启动子的结合来调节与核糖体生物发生相关的基因的表达,这是一种归因于盐分胁迫下核Ran水平降低的反式机制。我们的发现表明,Ran整合了核转运途径和转录调控网络,使酵母能够应对环境压力。
更新日期:2020-07-03
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