SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding.
SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding.
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DOI：
10.1126/science.aab0515
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发表时间：
2015-07-03
期刊：
影响因子：
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通讯作者：
Yen HC
中科院分区：
文献类型：
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作者：
Lin HC;Ho SC;Chen YY;Khoo KH;Hsu PH;Yen HC
硒代半胱氨酸（Sec）由密码子UGA翻译而来，通常是一个终止信号。密码子对偶扩展了遗传密码；然而，两种相互竞争的uga解码机制共存，立即损害了蛋白质组的保真度。我们报道了一个CRL2泛素连接酶介导的蛋白质量控制系统，该系统可以特异性地消除重分配失败导致的截断蛋白。将肽直接n端暴露于Sec（一种CRL2识别降解子），可促进蛋白质降解。Sec的掺入破坏了degron，保护读透蛋白不被CRL2检测到。我们的研究结果揭示了直接翻译终止和蛋白质水解辅助蛋白质质量控制之间的耦合，以及细胞应对有机硒摄入量波动的策略。
Selenocysteine (Sec) is translated from the codon UGA, typically a termination signal. Codon duality extends the genetic code; coexistence of two competing UGA-decoding mechanisms, however, immediately compromises proteome fidelity. Selenium availability tunes reassignment of UGA to Sec. We report a CRL2 ubiquitin ligase-mediated protein quality control system that specifically eliminates truncated proteins consequent of reassignment failures. Exposing the peptide immediately N-terminal to Sec, a CRL2 recognition degron, promotes protein degradation. Sec incorporation destroys the degron, protecting read-through proteins from detection by CRL2. Our findings reveal a coupling between directed translation termination and proteolysis-assisted protein quality control, as well as a cellular strategy to cope with fluctuations in organismal selenium intake.