Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue.
Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue.
复制标题
DOI：
10.1038/s41586-022-04487-6
复制
发表时间：
2022-03
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
--
作者：
核糖体在翻译过程中的停滞对细胞的适应性是有害的，但是这是如何被感知的，以及如何促进核糖体亚基的再循环和相关mRNA的质量控制以及不完整的新生链还知之甚少。在这里，我们发现枯草芽孢杆菌MutS 2，保守的MutS家族的ATP酶的功能在DNA错配修复作为一个意想不到的核糖体结合蛋白的翻译质量控制的重要功能的成员。亲和纯化的天然复合物的Cryo-EM分析揭示了MutS 2在感知停滞和翻译核糖体之间的碰撞中发挥作用，并表明核糖体碰撞如何作为部署下游过程的平台：MutS 2具有RNA内切核酸酶小MutS相关（SMR）结构域，以及适当定位以促进核糖体亚基解离的ATP酶/钳结构域，这是核糖体再循环和启动核糖体相关蛋白质质量控制（RQC）的要求。因此，Muts 2以ATP酶结构域依赖的方式促进具有丙氨酸尾脱序的新生链修饰-RQC的早期步骤。MutS 2和RQC基因在细菌门中强烈共存的证据强调了这些观察结果的相关性。总的来说，这些发现揭示了核糖体碰撞在开放阅读框架内对翻译中断的复杂反应中的深度保守作用。
Ribosome stalling during translation is detrimental to cellular fitness, but how this is sensed and elicits recycling of ribosomal subunits and quality control of associated mRNA and incomplete nascent-chains is poorly understood. Here we uncover Bacillus subtilis MutS2, a member of the conserved MutS-family of ATPases that function in DNA-mismatch repair as an unexpected ribosome-binding protein with an essential function in translational quality control. Cryo-EM analysis of affinity-purified native complexes reveals that MutS2 functions in sensing collisions between stalled and translating ribosomes and suggests how ribosome collisions can serve as platforms to deploy downstream processes: MutS2 has an RNA endonuclease Small MutS-Related (SMR) domain, as well as an ATPase/clamp domain that is properly positioned to promote ribosomal subunit dissociation, which is a requirement both for ribosome recycling and for initiating ribosome-associated protein quality control (RQC). Accordingly, Muts2 promotes nascent chain modification with Alanine-tail degrons—an early step in RQC—in an ATPase domain-dependent manner. The relevance of these observations is underscored by evidence of strong co-occurrence of MutS2 and RQC genes across bacterial phyla. Overall, the findings reveal a deeply-conserved role of ribosome collisions in mounting a complex response to the interruption of translation within open reading frames.
登录
查看更多内容
影响因子：
16
作者：
D'Orazio KN;Green R
通讯作者：
Green R
DOI：
10.4061/2011/691735
发表时间：
2011
期刊：
Molecular biology international
影响因子：
--
作者：
Fukui K;Kuramitsu S
通讯作者：
Kuramitsu S
影响因子：
16
作者：
Filbeck S;Cerullo F;Paternoga H;Tsaprailis G;Joazeiro CAP;Pfeffer S
通讯作者：
Pfeffer S
影响因子：
8.8
作者：
Glover, Marissa L.;Burroughs, A. Max;Arribere, Joshua A.
通讯作者：
Arribere, Joshua A.
影响因子：
16.6
作者：
Garzia, Aitor;Jafarnejad, Seyed Mehdi;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum