The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress.
The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress.
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DOI：
10.1016/j.celrep.2023.113359
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发表时间：
2023-11-28
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
氧化应激导致K63连接的泛素化的核糖体的E2泛素缀合酶Rad 6。然而，Rad 6介导的核糖体泛素化如何影响翻译尚不清楚。因此，我们在酿酒酵母中进行Ribo-seq和Disome-seq，并表明氧化应激导致核糖体在特定氨基酸基序处暂停，这也导致核糖体碰撞。然而，这些氧化还原暂停签名丢失在Rad 6的情况下，不依赖于核糖体相关的质量控制（RQC）途径。我们还表明，Rad 6是需要抑制整体翻译响应氧化应激，其删除导致抗氧化基因的表达增加。最后，我们观察到Rad 6的缺乏导致翻译过程中的变化，影响整合应激反应（ISR）途径的激活。我们的研究结果提供了一个高分辨率的图片在氧化应激过程中的基因表达变化，并解开一个额外的应激反应途径影响翻译延伸。Meydan等人发现了由泛素缀合酶Rad 6介导的翻译控制机制。在氧化应激过程中，延长核糖体暂停，同时使Ile-Pro肽键，和Rad 6的缺乏导致翻译的非经典重编程，暗示Rad 6作为应激反应的调节剂。
Oxidative stress causes K63-linked ubiquitination of ribosomes by the E2 ubiquitin conjugase Rad6. How Rad6-mediated ubiquitination of ribosomes affects translation, however, is unclear. We therefore perform Ribo-seq and Disome-seq in Saccharomyces cerevisiae and show that oxidative stress causes ribosome pausing at specific amino acid motifs, which also leads to ribosome collisions. However, these redox-pausing signatures are lost in the absence of Rad6 and do not depend on the ribosome-associated quality control (RQC) pathway. We also show that Rad6 is needed to inhibit overall translation in response to oxidative stress and that its deletion leads to increased expression of antioxidant genes. Finally, we observe that the lack of Rad6 leads to changes during translation that affect activation of the integrated stress response (ISR) pathway. Our results provide a high-resolution picture of the gene expression changes during oxidative stress and unravel an additional stress response pathway affecting translation elongation. Meydan et al. find a mechanism of translation control mediated by the ubiquitin conjugase Rad6. During oxidative stress, elongating ribosomes pause while making Ile-Pro peptide bonds, and the absence of Rad6 leads to non-canonical reprogramming of translation, implicating Rad6 as a regulator of the stress response.
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DOI：
10.1261/rna.078964.121
发表时间：
2022-03
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Houston L;Platten EM;Connelly SM;Wang J;Grayhack EJ
通讯作者：
Grayhack EJ
X连锁的智力残疾型Nascimento是一种临床上不同的，可能未被诊断的实体。
影响因子：
3.7
作者：
Czeschik JC;Bauer P;Buiting K;Dufke C;Guillén-Navarro E;Johnson DS;Koehler U;López-González V;Lüdecke HJ;Male A;Morrogh D;Rieß A;Tzschach A;Wieczorek D;Kuechler A
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Kuechler A
影响因子：
10.5
作者：
Cherkasova, VA;Hinnebusch, AG
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Hinnebusch, AG
影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
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Ron, D
影响因子：
64.5
作者：
Guydosh NR;Green R
通讯作者：
Green R