Release of Ubiquitinated and Non-ubiquitinated Nascent Chains from Stalled Mammalian Ribosomal Complexes by ANKZF1 and Ptrh1
Release of Ubiquitinated and Non-ubiquitinated Nascent Chains from Stalled Mammalian Ribosomal Complexes by ANKZF1 and Ptrh1
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DOI：
10.1016/j.molcel.2018.08.022
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发表时间：
2018-10-18
期刊：
影响因子：
16
通讯作者：
Pestova, Tatyana V.
中科院分区：
文献类型：
--
作者：
Kuroha, Kazushige;Zinoviev, Alexandra;Pestova, Tatyana V.
核糖体相关质量控制（RQC）途径降解由中断的翻译产生的新生链（NC）。首先，再循环因子分裂停滞的核糖体，产生NC-tRNA/60 S核糖体新生链复合物（60 S RNC）。60 S RNC与NEMF相关联，NEMF招募泛素化NC的E3泛素连接酶Listerin。Ub-NC随后的核糖体释放机制仍然不清楚。我们发现，在非泛素化的60 S RNC和80 S RNC上形成的非终止mRNA中，tRNA没有牢固地固定在P位点，这使得肽基-tRNA水解酶Ptrh 1能够切割NC-tRNA，这表明存在一种涉及非泛素化NC释放的途径。与NEMF和Listerin的结合以及NC的泛素化导致NC-tRNA的适应，使60 S RNC对Ptrh 1具有抗性，但对ANKZF 1敏感，ANKZF 1诱导tRNA受体臂中的特异性切割，释放与4个3 '末端tRNA核苷酸连接的蛋白酶体可降解的Ub-NC。我们还发现，TCF 25，一个不好的特点RQC组件，确保优先形成的K48-泛素连接。
The ribosome-associated quality control (RQC) pathway degrades nascent chains (NCs) arising from interrupted translation. First, recycling factors split stalled ribosomes, yielding NC-tRNA/60S ribosome-nascent chain complexes (60S RNCs). 60S RNCs associate with NEMF, which recruits the E3 ubiquitin ligase Listerin that ubiquitinates NCs. The mechanism of subsequent ribosomal release of Ub-NCs remains obscure. We found that, in non-ubiquitinated 60S RNCs and 80S RNCs formed on non-stop mRNAs, tRNA is not firmly fixed in the P site, which allows peptidyl-tRNA hydrolase Ptrh1 to cleave NC-tRNA, suggesting the existence of a pathway involving release of non-ubiquitinated NCs. Association with NEMF and Listerin and ubiquitination of NCs results in accommodation of NC-tRNA, rendering 60S RNCs resistant to Ptrh1 but susceptible to ANKZF1, which induces specific cleavage in the tRNA acceptor arm, releasing proteasome-degradable Ub-NCs linked to four 3'-terminal tRNA nucleotides. We also found that TCF25, a poorly characterized RQC component, ensures preferential formation of the K48-ubiquitin linkage.