Oxidation and alkylation stresses activate ribosome-quality control
Oxidation and alkylation stresses activate ribosome-quality control
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DOI：
10.1038/s41467-019-13579-3
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发表时间：
2019-12-09
影响因子：
16.6
通讯作者：
Zaher, Hani S.
中科院分区：
文献类型：
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作者：
Yan, Liewei L.;Simms, Carrie L.;Zaher, Hani S.
已知核碱基的氧化和烷基化会破坏它们在RNA内的碱基配对特性。然而，目前尚不清楚生物体是否已经进化出应对这种损害的一般机制。在这里，我们表明，mRNA的监视途径的不去衰变和相关的核糖体质量控制被激活，在响应核碱基烷基化和氧化。我们的研究结果表明，这些过程是重要的清除化学修饰的mRNA和由此产生的异常蛋白产物。在缺乏Xrn1的情况下，受损mRNA的水平显著增加。此外，LTN1的缺失导致在氧化剂和烷基化剂存在下蛋白质聚集体的积累。这种积累伴随着核糖体蛋白的Hel2依赖性调节性遍在化。总的来说，我们的数据突出了化学损伤的mRNA对细胞内稳态的负担，并表明生物体进化出了对抗其积累的机制。
Oxidation and alkylation of nucleobases are known to disrupt their base-pairing properties within RNA. It is, however, unclear whether organisms have evolved general mechanism(s) to deal with this damage. Here we show that the mRNA-surveillance pathway of no-go decay and the associated ribosome-quality control are activated in response to nucleobase alkylation and oxidation. Our findings reveal that these processes are important for clearing chemically modified mRNA and the resulting aberrant-protein products. In the absence of Xrn1, the level of damaged mRNA significantly increases. Furthermore, deletion of LTN1 results in the accumulation of protein aggregates in the presence of oxidizing and alkylating agents. This accumulation is accompanied by Hel2-dependent regulatory ubiquitylation of ribosomal proteins. Collectively, our data highlight the burden of chemically damaged mRNA on cellular homeostasis and suggest that organisms evolved mechanisms to counter their accumulation.