The structure of a di-ribosome (disome) as a unit for RQC and NGD quality control pathways recognition.
The structure of a di-ribosome (disome) as a unit for RQC and NGD quality control pathways recognition.
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作为 RQC 和 NGD 质量控制途径识别单元的二核糖体 (disome) 的结构。
DOI：
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
T. Inada
中科院分区：
文献类型：
--
作者：
Ken Ikeuchi;P. Tesina;Y. Matsuo;Takato Sugiyama;Jingdong Cheng;Y. Saeki;Keiji Tanaka;T. Becker;R. Beckmann;T. Inada
摘要核糖体停滞触发了针对mRNA（NGD：无衰变）和新生多肽（RQC：核糖体相关质量控制）的质量控制途径。RQC需要Hel 2依赖性uS 10泛素化和酵母中的RQT复合物。在这里，我们报告了Hel 2依赖的uS 10泛素化和Slh 1/Rqt 2对于二核糖体（二体）单位内的RQC和NGD诱导至关重要，该单位由领先的停滞核糖体和随后的碰撞核糖体组成。在体外翻译反应中，Hel 2优先泛素化质量控制诱导报告mRNA上的二体而不是单体。对二体单元的Cryo-EM分析揭示了适合于Hel 2识别和修饰的独特结构排列。RQT复合物或uS 10泛素化的缺乏导致二体单元内NGD的消除。相反，我们观察到Hel 2介导的二体上游裂解，由初始Not 4介导的eS 7单泛素化和随后Hel 2介导的K63连接的多聚泛素化控制。我们认为Hel 2介导的核糖体泛素化是典型NGD（NGD RQC +）和与二体偶联的RQC所必需的，而二体外的RQC-未偶联的NGD（NGD RQC-）可以以Not 4依赖的方式发生。
Abstract Ribosome stalling triggers quality control pathways targeting the mRNA (NGD: no‐go decay) and the nascent polypeptide (RQC: ribosome‐associated quality control). RQC requires Hel2‐dependent uS10 ubiquitination and the RQT complex in yeast. Here, we report that Hel2‐dependent uS10 ubiquitination and Slh1/Rqt2 are crucial for RQC and NGD induction within a di‐ribosome (disome) unit, which consists of the leading stalled ribosome and the following colliding ribosome. Hel2 preferentially ubiquitinated a disome over a monosome on a quality control inducing reporter mRNA in an in vitro translation reaction. Cryo‐EM analysis of the disome unit revealed a distinct structural arrangement suitable for recognition and modification by Hel2. The absence of the RQT complex or uS10 ubiquitination resulted in the elimination of NGD within the disome unit. Instead, we observed Hel2‐mediated cleavages upstream of the disome, governed by initial Not4‐mediated monoubiquitination of eS7 and followed by Hel2‐mediated K63‐linked polyubiquitination. We propose that Hel2‐mediated ribosome ubiquitination is required both for canonical NGD (NGD RQC + ) and RQC coupled to the disome and that RQC‐uncoupled NGD outside the disome (NGD RQC − ) can occur in a Not4‐dependent manner.
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DOI：
10.1261/rna.060897.117
发表时间：
2017-05
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Sitron CS;Park JH;Brandman O
通讯作者：
Brandman O
影响因子：
16
作者：
Sundaramoorthy E;Leonard M;Mak R;Liao J;Fulzele A;Bennett EJ
通讯作者：
Bennett EJ
影响因子：
4.5
作者：
Inada, T;Winstall, E;Sachs, AB
通讯作者：
Sachs, AB
影响因子：
16
作者：
Simms CL;Yan LL;Zaher HS
通讯作者：
Zaher HS
影响因子：
5.7
作者：
Svidritskiy, Egor;Brilot, Axel F.;Koh, Cha San;Grigorieff, Nikolaus;Korostelev, Andrei A.
通讯作者：
Korostelev, Andrei A.