The non-stop decay mRNA surveillance pathway is required for oxidative stress tolerance.
The non-stop decay mRNA surveillance pathway is required for oxidative stress tolerance.
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DOI：
10.1093/nar/gkx306
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发表时间：
2017-06-20
影响因子：
14.9
通讯作者：
Grant CM
中科院分区：
文献类型：
--
作者：
Jamar NH;Kritsiligkou P;Grant CM
活性氧（ROS）是正常有氧代谢的有毒副产物。ROS可以破坏mrna和翻译装置，导致翻译缺陷和异常蛋白的产生。三种mRNA质量控制系统监测mRNA的翻译错误：无义介导的衰变，不间断衰变（NSD）和不去衰变（NGD）途径。在这里，我们表明识别NSD底物和SKI复合物组分所需的因子是氧化耐受性所必需的。我们发现了sk7和NGD组分（Dom34/Hbs1）的重叠需求，sk7连接了SKI复合物和外泌体之间的相互作用，而NGD组分（Dom34/Hbs1）已被证明在NSD和NGD中都起作用。我们发现sk7 dom34和sk7 hbs1突变体对过氧化氢胁迫敏感，并积累NSD底物。我们进一步表明，在ROS暴露期间，由于Sup35翻译终止因子的聚集而产生NSD底物，这增加了停止密码子的读取，从而允许核糖体翻译成mrna的3΄-end。过表达Sup35减少停止密码子的通读，并恢复与该模型一致的氧化耐受性。我们的数据揭示了氧化应激条件下对NSD途径的意外需求，这可以防止NSD mrna产生异常蛋白。
Reactive oxygen species (ROS) are toxic by-products of normal aerobic metabolism. ROS can damage mRNAs and the translational apparatus resulting in translational defects and aberrant protein production. Three mRNA quality control systems monitor mRNAs for translational errors: nonsense-mediated decay, non-stop decay (NSD) and no-go decay (NGD) pathways. Here, we show that factors required for the recognition of NSD substrates and components of the SKI complex are required for oxidant tolerance. We found an overlapping requirement for Ski7, which bridges the interaction between the SKI complex and the exosome, and NGD components (Dom34/Hbs1) which have been shown to function in both NSD and NGD. We show that ski7 dom34 and ski7 hbs1 mutants are sensitive to hydrogen peroxide stress and accumulate an NSD substrate. We further show that NSD substrates are generated during ROS exposure as a result of aggregation of the Sup35 translation termination factor, which increases stop codon read-through allowing ribosomes to translate into the 3΄-end of mRNAs. Overexpression of Sup35 decreases stop codon read-through and rescues oxidant tolerance consistent with this model. Our data reveal an unanticipated requirement for the NSD pathway during oxidative stress conditions which prevents the production of aberrant proteins from NSD mRNAs.