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

  • Science. 2015 Jul 3;349(6243):91-5. doi: 10.1126/science.aab0515.
Hsiu-Chuan Lin  1 ,  Szu-Chi Ho  2 ,  Yi-Yun Chen  3 ,  Kay-Hooi Khoo  4 ,  Pang-Hung Hsu  5 ,  Hsueh-Chi S Yen  1
Affiliations
  • 1. Institute of Molecular Biology, Academia Sinica, Taiwan. Genome and Systems Biology Degree Program, National Taiwan University, Taiwan.
  • 2. Institute of Molecular Biology, Academia Sinica, Taiwan.
  • 3. Institute of Biological Chemistry, Academia Sinica, Taiwan.
  • 4. Genome and Systems Biology Degree Program, National Taiwan University, Taiwan. Institute of Biological Chemistry, Academia Sinica, Taiwan.
  • 5. Department of Life Science, Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Taiwan.
PMID: 26138980 DOI: 10.1126/science.aab0515
Abstract

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.