Novel structural determinants in human SECIS elements modulate the translational recoding of UGA as selenocysteine.

Centre de recherche de Gif-sur-Yvette, FRC 3115, Centre de Génétique Moléculaire, CNRS, FRE 3144, Gif-sur-Yvette, F-75005 Paris, France.
Nucleic Acids Research (Impact Factor: 8.28). 09/2009; 37(17):5868-80. DOI: 10.1093/nar/gkp635
Source: PubMed

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.

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