Ubiquitination of stalled ribosome triggers ribosome-associated quality control.
Ubiquitination of stalled ribosome triggers ribosome-associated quality control.
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DOI：
10.1038/s41467-017-00188-1
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发表时间：
2017-07-31
影响因子：
16.6
通讯作者：
Inada T
中科院分区：
文献类型：
--
作者：
Matsuo Y;Ikeuchi K;Saeki Y;Iwasaki S;Schmidt C;Udagawa T;Sato F;Tsuchiya H;Becker T;Tanaka K;Ingolia NT;Beckmann R;Inada T
多碱基序列的翻译停滞导致核糖体停滞，停滞产物被核糖体介导的质量控制(RQC)系统降解。在这里，我们报告了RQC需要E3泛素连接酶Hel2(或RQT1)泛素化40S核糖体蛋白US10。我们鉴定了一个RQC触发器(RQT)亚复合体，它由RNA解旋酶家族蛋白Slh1/Rqt2、泛素结合蛋白Cue3/Rqt3和RQC所需的yKR023W/Rqt4组成。RQT突变体在RQC中的缺陷与其对茴香霉素的敏感性有关，后者使核糖体以旋转形式停滞。冷冻电子显微镜分析表明，与Hel2结合的核糖体主要是与杂交tRNAs一起旋转的形式。核糖体图谱显示，核糖体在旋转状态停滞，在P-A位点有特定的密码子对作为RQC底物。Rqt1特异性地泛化这些停滞的核糖体，使其靶向RQT复合体，从而允许随后的RQC反应，包括将停滞的核糖体解离成亚单位。几种蛋白质质量控制机制已经到位，以触发异常多肽和mRNAs的快速降解。在这里，作者描述了一种核糖体介导的质量控制机制，涉及E3泛素连接酶Hel2/RQT1泛素化核糖体蛋白。
Translation arrest by polybasic sequences induces ribosome stalling, and the arrest product is degraded by the ribosome-mediated quality control (RQC) system. Here we report that ubiquitination of the 40S ribosomal protein uS10 by the E3 ubiquitin ligase Hel2 (or RQT1) is required for RQC. We identify a RQC-trigger (RQT) subcomplex composed of the RNA helicase-family protein Slh1/Rqt2, the ubiquitin-binding protein Cue3/Rqt3, and yKR023W/Rqt4 that is required for RQC. The defects in RQC of the RQT mutants correlate with sensitivity to anisomycin, which stalls ribosome at the rotated form. Cryo-electron microscopy analysis reveals that Hel2-bound ribosome are dominantly the rotated form with hybrid tRNAs. Ribosome profiling reveals that ribosomes stalled at the rotated state with specific pairs of codons at P-A sites serve as RQC substrates. Rqt1 specifically ubiquitinates these arrested ribosomes to target them to the RQT complex, allowing subsequent RQC reactions including dissociation of the stalled ribosome into subunits. Several protein quality control mechanisms are in place to trigger the rapid degradation of aberrant polypeptides and mRNAs. Here the authors describe a mechanism of ribosome-mediated quality control that involves the ubiquitination of ribosomal proteins by the E3 ubiquitin ligase Hel2/RQT1.
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影响因子：
3.8
作者：
Chi, P;Van Komen, S;Sung, P
通讯作者：
Sung, P
核糖体质量控制是暴露于脱氧烯醇和毛刺素的酵母中心保护机制。
影响因子：
4.4
作者：
Kugler KG;Jandric Z;Beyer R;Klopf E;Glaser W;Lemmens M;Shams M;Mayer K;Adam G;Schüller C
通讯作者：
Schüller C
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：
10.5
作者：
Fujii, Kotaro;Kitabatake, Makoto;Ohno, Mutsuhito
通讯作者：
Ohno, Mutsuhito