Article

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: 9.11). 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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Available from: Laurent Chavatte, May 22, 2015
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    • "SECIS elements are classified into two types based on the occurrence of a mini-stem within the apical loop (Figure 1A). However, belonging to a particular SECIS class does not necessarily characterize SECIS ‘strength’—the ability to efficiently insert Sec (10). As a rule, most Type II SECIS elements are predicted to be more thermodynamically stable than Type I structures. "
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    ABSTRACT: It is thought that the SelenoCysteine Insertion Sequence (SECIS) element and UGA codon are sufficient for selenocysteine (Sec) insertion. However, we found that UGA supported Sec insertion only at its natural position or in its close proximity in mammalian thioredoxin reductase 1 (TR1). In contrast, Sec could be inserted at any tested position in mammalian TR3. Replacement of the 3′-UTR of TR3 with the corresponding segment of a Euplotes crassus TR restricted Sec insertion into the C-terminal region, whereas the 3′-UTR of TR3 conferred unrestricted Sec insertion into E. crassus TR, in which Sec insertion is normally limited to the C-terminal region. Exchanges of 3′-UTRs between mammalian TR1 and E. crassus TR had no effect, as both proteins restricted Sec insertion. We further found that these effects could be explained by the use of selenoprotein-specific SECIS elements. Examination of Sec insertion into other selenoproteins was consistent with this model. The data indicate that mammals evolved the ability to limit Sec insertion into natural positions within selenoproteins, but do so in a selenoprotein-specific manner, and that this process is controlled by the SECIS element in the 3′-UTR.
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    • "One quarter of all human selenoproteins share a similar placement of their Sec residue in the C-terminus (SelS, SelK, SelO, TrxR1, TrxR2 and TrxR3) [57]. Of this subset, SelS, SelO and TrxR3 are in the group of six SECIS elements identified as weak with respect to their UGA-recoding activity [54]. TrxR1 SECIS activity was on the lowest end of the moderate class. "
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    • "The SECIS elements in trout GPx1/2 genes contain the non-Watson-Crick base pairs 5 TGAA3 :5 TGAT3 , whilst 5 TGAC3 :5 TGAT3 is present in the trout GPx4 isoforms. All the GPx isoforms possess two apical loops and hence they belong to the type II group of selenoproteins (Latrèche, 2009). The predicted polypeptides of the trout GPxs were aligned with GPx proteins from fish and mammals. "
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