Alanine Tails Signal Proteolysis in Bacterial Ribosome-Associated Quality Control
Alanine Tails Signal Proteolysis in Bacterial Ribosome-Associated Quality Control
复制标题
DOI：
10.1016/j.cell.2019.05.002
复制
发表时间：
2019-06-27
期刊：
影响因子：
64.5
通讯作者：
Joazeiro, Claudio A. P.
中科院分区：
文献类型：
--
作者：
Lytvynenko, Iryna;Paternoga, Helge;Joazeiro, Claudio A. P.
在核糖体相关质量控制（RQC）中，Rqc 2/NEMF密切支持E3连接酶Ltn 1/listerin促进泛素化和降解阻碍大（60 S）核糖体亚基的异常起始链-核糖体在翻译期间停滞的产物。然而，虽然Ltn 1是真核生物特异性的，但Rqc 2同源物也在细菌和古细菌中发现;原核生物Rqc 2是否具有RQC相关功能仍然未知。在这里，我们表明，在真核生物中，细菌Rqc 2同源物（RqcH）识别受阻50 S亚基，促进初生链蛋白水解。出乎意料的是，RqcH通过附加C-末端聚丙氨酸尾部（其充当由ClpXP蛋白酶识别的降解决定子）以直接方式标记用于降解的初生链。此外，RqcH与tmRNA/ssrA冗余地起作用，并保护细胞免受翻译和环境应激。我们的研究结果揭示了一种蛋白水解标记机制，其对真核生物中相关修饰的功能具有影响，并表明RQC在最后一个通用共同祖先（LUCA）中已经很活跃，以帮助科普不完整的翻译。
In ribosome-associated quality control (RQC), Rqc2/NEMF closely supports the E3 ligase Ltn1/listerin in promoting ubiquitylation and degradation of aberrant nascent-chains obstructing large (60S) ribosomal subunits-products of ribosome stalling during translation. However, while Ltn1 is eukaryote-specific, Rqc2 homologs are also found in bacteria and archaea; whether prokaryotic Rqc2 has an RQC-related function has remained unknown. Here, we show that, as in eukaryotes, a bacterial Rqc2 homolog (RqcH) recognizes obstructed 50S subunits and promotes nascent-chain proteolysis. Unexpectedly, RqcH marks nascent-chains for degradation in a direct manner, by appending C-terminal poly-alanine tails that act as degrons recognized by the CIpXP protease. Furthermore, RqcH acts redundantly with tmRNA/ssrA and protects cells against translational and environmental stresses. Our results uncover a proteolytic-tagging mechanism with implications toward the function of related modifications in eukaryotes and suggest that RQC was already active in the last universal common ancestor (LUCA) to help cope with incomplete translation.