title: Novel structural determinants in human SECIS elements modulate the translational recoding of UGA as selenocysteine.
abstract: The selenocysteine insertion sequence (SECIS) element directs the translational recoding of UGA as selenocysteine. In eukaryotes, the SECIS is located downstream of the UGA codon in the 3'-UTR of the selenoprotein mRNA. Despite poor sequence conservation, all SECIS elements form a similar stem-loop structure containing a putative kink-turn motif. We functionally characterized the 26 SECIS elements encoded in the human genome. Surprisingly, the SECIS elements displayed a wide range of UGA recoding activities, spanning several 1000-fold in vivo and several 100-fold in vitro. The difference in activity between a representative strong and weak SECIS element was not explained by differential binding affinity of SECIS binding Protein 2, a limiting factor for selenocysteine incorporation. Using chimeric SECIS molecules, we identified the internal loop and helix 2, which flank the kink-turn motif, as critical determinants of UGA recoding activity. The simultaneous presence of a GC base pair in helix 2 and a U in the 5'-side of the internal loop was a statistically significant predictor of weak recoding activity. Thus, the SECIS contains intrinsic information that modulates selenocysteine incorporation efficiency.
authors: Centre de recherche de Gif-sur-Yvette, FRC 3115, Centre de Génétique Moléculaire, CNRS, FRE 3144, Gif-sur-Yvette, F-75005 Paris, France.
authors: Lynda
authors: L
authors: Latrèche
authors: Olivier
authors: O
authors: Jean-Jean
authors: Donna M
authors: DM
authors: Driscoll
authors: Laurent
authors: L
authors: Chavatte
mesh_terms: D020413:3' Untranslated Regions / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D018388:Codon, Terminator; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism; D017279:Selenocysteine / Q000378:metabolism*; D017423:Sequence Analysis, RNA
chemical_list: D020413:3' Untranslated Regions; D018388:Codon, Terminator; D016601:RNA-Binding Proteins; C119984:selenocysteine insertion sequence binding protein, mammalian; D017279:Selenocysteine