Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis.
Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis.
复制标题
冷却诱导的exosc10的Sumoylation下调核糖体生物发生。
DOI：
10.1261/rna.054411.115
复制
发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Willis AE
中科院分区：
文献类型：
--
作者：
Knight JR;Bastide A;Peretti D;Roobol A;Roobol J;Mallucci GR;Smales CM;Willis AE
RNA 外泌体对于真核细胞中功能性 RNA 种类的 3' 加工和异常 RNA 的降解至关重要。最近的报告定义了外泌体催化结构域的底物并解决了外泌体复合物的多聚体结构。然而，外泌体活性的调节仍然知之甚少，特别是在响应生理应激方面。观察到哺乳动物细胞的冷却会导致 40S:60S 核糖体亚基比例降低，我们发现了温度降低对核外泌体的调节。使用人体细胞和允许全身冷却的体内模型系统，我们观察到寒冷中 EXOSC10（hRrp6、Pm/Scl-100）表达减少。同时，两种冷却模型都会增加全局 SUMO 化，从而识别出 SUMO1 与 EXOSC10 的特定缀合，这是一个通过冷却而增加的过程。此外，我们通过诱变定义了 EXOSC10 中的主要 SUMO 化位点，并表明仅过度表达 SUMO1 就足以抑制 EXOSC10 丰度。在人类细胞中通过 RNAi 减少 EXOSC10 表达与寒冷中观察到的 3' 前核糖体 RNA 加工缺陷以及降低 40S:60S 比例相关，这是 EXOSC10 抑制之前未表征的结果。总之，这项工作说明 EXOSC10 可以通过 SUMOylation 进行修饰，并识别出这种调节在体外和体内均普遍存在的生理应激。
The RNA exosome is essential for 3′ processing of functional RNA species and degradation of aberrant RNAs in eukaryotic cells. Recent reports have defined the substrates of the exosome catalytic domains and solved the multimeric structure of the exosome complex. However, regulation of exosome activity remains poorly characterized, especially in response to physiological stress. Following the observation that cooling of mammalian cells results in a reduction in 40S:60S ribosomal subunit ratio, we uncover regulation of the nuclear exosome as a result of reduced temperature. Using human cells and an in vivo model system allowing whole-body cooling, we observe reduced EXOSC10 (hRrp6, Pm/Scl-100) expression in the cold. In parallel, both models of cooling increase global SUMOylation, leading to the identification of specific conjugation of SUMO1 to EXOSC10, a process that is increased by cooling. Furthermore, we define the major SUMOylation sites in EXOSC10 by mutagenesis and show that overexpression of SUMO1 alone is sufficient to suppress EXOSC10 abundance. Reducing EXOSC10 expression by RNAi in human cells correlates with the 3′ preribosomal RNA processing defects seen in the cold as well as reducing the 40S:60S ratio, a previously uncharacterized consequence of EXOSC10 suppression. Together, this work illustrates that EXOSC10 can be modified by SUMOylation and identifies a physiological stress where this regulation is prevalent both in vitro and in vivo.