title: SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding.
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.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taiwan. Genome and Systems Biology Degree Program, National Taiwan University, Taiwan.
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taiwan.
authors.forename: Szu-Chi
authors.initials: SC
authors.lastname: Ho
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taiwan.
authors.forename: Yi-Yun
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Genome and Systems Biology Degree Program, National Taiwan University, Taiwan. Institute of Biological Chemistry, Academia Sinica, Taiwan.
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
authors.affiliation: Department of Life Science, Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Taiwan.
authors.forename: Pang-Hung
authors.initials: PH
authors.lastname: Hsu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taiwan. Genome and Systems Biology Degree Program, National Taiwan University, Taiwan.
authors.forename: Hsueh-Chi S
authors.initials: HC
authors.lastname: Yen
mesh_terms: D018388:Codon, Terminator; D057809:HEK293 Cells; D006801:Humans; D010443:Peptide Chain Termination, Translational / Q000235:genetics*; D059748:Proteolysis; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D012643:Selenium / Q000378:metabolism; D017279:Selenocysteine / Q000235:genetics / Q000378:metabolism*; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D018388:Codon, Terminator; D051140:Selenoproteins; D025801:Ubiquitin; D017279:Selenocysteine; D044843:SKP Cullin F-Box Protein Ligases; D012643:Selenium