ZNF598 Is a Quality Control Sensor of Collided Ribosomes.
ZNF598 Is a Quality Control Sensor of Collided Ribosomes.
复制标题
DOI：
10.1016/j.molcel.2018.08.037
复制
发表时间：
2018-11-01
期刊：
影响因子：
16
通讯作者：
Hegde RS
中科院分区：
文献类型：
--
作者：
Juszkiewicz S;Chandrasekaran V;Lin Z;Kraatz S;Ramakrishnan V;Hegde RS
异常缓慢的翻译启动了由泛素连接酶ZNF 598启动的质量控制途径。ZNF 598如何区分生理性和病理性翻译复合物，并选择性地泛素化停滞的核糖体尚不清楚。在这里，我们发现ZNF 598参与的最小单位是碰撞的二核糖体，当尾随核糖体遇到较慢的前导核糖体时，会产生一种分子物种。碰撞的二核糖体结构揭示了ZNF 598的泛素化靶点所在的广泛的40 S-40 S界面。60 S相互作用的缺乏允许不同的核糖体旋转状态，解释了为什么ZNF 598识别与领先的核糖体如何停滞无关。使用核糖体碰撞作为停滞的代理，允许通过mRNA的起始速率来调整可容忍的减速程度;因此，触发质量控制的阈值是底物特异性的。这些发现说明了细胞因子如何利用高阶核糖体结构来监测翻译状态。ZNF 598是许多无关原因引起的核糖体碰撞的直接传感器ZNF 598识别和泛素化的最小靶点是碰撞的双核糖体碰撞的双核糖体结构表明ZNF 598泛素位点靠近界面以ZNF 598依赖的方式终止翻译需要碰撞细胞含有数百万个核糖体，需要精确翻译mRNA以维持稳态。翻译过程中过度减速的核糖体必须迅速解决，以避免疾病。Juszkiewicz等人显示核糖体碰撞，异常翻译的标志，被泛素连接酶ZNF 598检测到以启动质量控制。
Aberrantly slow translation elicits quality control pathways initiated by the ubiquitin ligase ZNF598. How ZNF598 discriminates physiologic from pathologic translation complexes and ubiquitinates stalled ribosomes selectively is unclear. Here, we find that the minimal unit engaged by ZNF598 is the collided di-ribosome, a molecular species that arises when a trailing ribosome encounters a slower leading ribosome. The collided di-ribosome structure reveals an extensive 40S-40S interface in which the ubiquitination targets of ZNF598 reside. The paucity of 60S interactions allows for different ribosome rotation states, explaining why ZNF598 recognition is indifferent to how the leading ribosome has stalled. The use of ribosome collisions as a proxy for stalling allows the degree of tolerable slowdown to be tuned by the initiation rate on that mRNA; hence, the threshold for triggering quality control is substrate specific. These findings illustrate how higher-order ribosome architecture can be exploited by cellular factors to monitor translation status. ZNF598 is a direct sensor of ribosome collisions incurred by many unrelated causes The minimal target recognized and ubiquitinated by ZNF598 is a collided di-ribosome Collided di-ribosome structure shows that ZNF598 ubiquitin sites are near the interface Collisions are required to terminally arrest translation in ZNF598-dependent manner Cells contain millions of ribosomes that need to translate mRNAs accurately to maintain homeostasis. Ribosomes that slow excessively during translation must be promptly resolved to avoid disease. Juszkiewicz et al. show that ribosome collisions, a sign of aberrant translation, are detected by the ubiquitin ligase ZNF598 to initiate quality control.
登录
查看更多内容
影响因子：
14.9
作者：
Afonina ZA;Myasnikov AG;Shirokov VA;Klaholz BP;Spirin AS
通讯作者：
Spirin AS
DOI：
10.1073/pnas.0812819106
发表时间：
2009-02-17
影响因子：
11.1
作者：
Chu, Jessie;Hong, Nancy A.;Kay, Steve A.
通讯作者：
Kay, Steve A.
影响因子：
4.8
作者：
Dimitrova, Lyudmila N.;Kuroha, Kazushige;Inada, Toshifumi
通讯作者：
Inada, Toshifumi
影响因子：
16.6
作者：
Garzia, Aitor;Jafarnejad, Seyed Mehdi;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum
影响因子：
16
作者：
Higgins, Renee;Gendron, Joshua M.;Rising, Lisa;Mak, Raymond;Webb, Kristofor;Kaiser, Stephen E.;Zuzow, Nathan;Riviere, Paul;Yang, Bing;Fenech, Emma;Tang, Xin;Lindsay, Scott A.;Christianson, John C.;Hampton, Randolph Y.;Wasserman, Steven A.;Bennett, Eric J.
通讯作者：
Bennett, Eric J.