SIRT1 Functions as a Negative Regulator of Eukaryotic Poly(A)RNA Transport
SIRT1 Functions as a Negative Regulator of Eukaryotic Poly(A)RNA Transport
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SIRT1 作为真核 Poly(A)RNA 运输的负调节因子
DOI：
10.1016/j.cub.2017.06.040
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发表时间：
2017
期刊：
影响因子：
9.2
通讯作者：
Wang Chuangui
中科院分区：
文献类型：
--
作者：
Shan Peipei;Fan Guangjian;Sun Lianhui;Liu Jinqin;Wang Weifang;Hu Chen;Zhang Xiaohong;Zhai Qiwei;Song Xiaoyu;Cao Liu;Cui Yongping;Zhang Shengping;Wang Chuangui
大多数真核生物的mRNA在细胞核中被多聚腺苷酸化，并且poly（A）-尾是有效的mRNA输出和翻译所必需的。然而，mRNA转运的机制仍不清楚。在这里，我们报告说，烟酰胺腺嘌呤二核苷酸（NAD）依赖性脱乙酰酶SIRT 1作为一个能量传感器和负调节聚（A）RNA转运通过脱乙酰化聚（A）结合蛋白，PABP 1。在能量饥饿时，SIRT 1与PABP 1相互作用并使其脱乙酰化，并使其poly（A）RNA结合失活，导致PABP 1和poly（A）RNA在核中积累，从而促进真核细胞减弱蛋白质合成和能量消耗以适应能量应激。此外，AMPK介导的SIRT 1磷酸化是能量饥饿诱导的PABP 1-SIRT 1缔合、PABP 1脱乙酰化和poly（A）RNA核保留所必需的。此外，SIRT 1-PABP 1的关联不是能量饥饿所特有的，而是一种常见的应激反应。这些观察结果提供了对真核生物mRNA转运和翻译的动态调节的见解，表明poly（A）-尾也为真核生物有效地关闭成熟mRNA转运并从而定制蛋白质合成以维持应激条件下的能量稳态提供了基础。
Most eukaryotic mRNAs are polyadenylated in the nucleus, and the poly(A)-tail is required for efficient mRNA export and translation. However, mechanisms governing mRNA transport remain unclear. Here, we report that the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1 acts as an energy sensor and negatively regulates poly(A)RNA transport via deacetylating a poly(A)-binding protein, PABP1. Upon energy starvation, SIRT1 interacts with and deacetylates PABP1 and deactivates its poly(A)RNA binding, leading to nuclear accumulation of PABP1 and poly(A)RNA and thus facilitating eukaryotic cells to attenuate protein synthesis and energy consumption to adapt to energy stress. Moreover, AMPK-directed SIRT1 phosphorylation is required for energy starvation-induced PABP1-SIRT1 association, PABP1 deacetylation, and poly(A)RNA nuclear retention. In addition, the SIRT1-PABP1 association is not specific to energy starvation but represents a common stress response. These observations provide insights into dynamic modulation of eukaryotic mRNA transport and translation, suggesting that the poly(A)-tail also provides a basis for eukaryotes to effectively shut down mature mRNA transport and thereby tailor protein synthesis to maintain energy homeostasis under stress conditions.