CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding

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Science  03 Jul 2015:
Vol. 349, Issue 6243, pp. 91-95
DOI: 10.1126/science.aab0515

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Clearing out selenoprotein garbage

Our DNA consists of codons that code for 20 different amino acids. Another amino acid, selenocysteine, is also found in several human selenoproteins. Selenocysteine is incorporated through the recoding of a stop codon, but failures in this process result in premature termination of protein synthesis. Lin et al. showed that the potentially dangerous truncated proteins formed in such cases are specifically degraded by a protein quality surveillance system. The surveillance system can specifically recognize the truncated ends of the various prematurely terminated selenoproteins and target their destruction.

Science, this issue p. 91


Selenocysteine (Sec) is translated from the codon UGA, typically a termination signal. Codon duality extends the genetic code; however, the coexistence of two competing UGA-decoding mechanisms immediately compromises proteome fidelity. Selenium availability tunes the reassignment of UGA to Sec. We report a CRL2 ubiquitin ligase–mediated protein quality-control system that specifically eliminates truncated proteins that result from 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.

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