Selenium, an essential trace element, is incorporated into selenoproteins as 
selenocysteine (Sec), the 21st amino acid. In order to synthesize 
selenoproteins, a translational reprogramming event must occur since Sec is 
encoded by the UGA stop codon. In mammals, the recoding of UGA as Sec depends on 
the selenocysteine insertion sequence (SECIS) element, a stem-loop structure in 
the 3' untranslated region of the transcript. The SECIS acts as a platform for 
RNA-binding proteins, which mediate or regulate the recoding mechanism. Using UV 
crosslinking, we identified a 110 kDa protein, which binds with high affinity to 
SECIS elements from a subset of selenoprotein mRNAs. The crosslinking activity 
was purified by RNA affinity chromatography and identified as nucleolin by mass 
spectrometry analysis. In vitro binding assays showed that purified nucleolin 
discriminates among SECIS elements in the absence of other factors. Based on 
siRNA experiments, nucleolin is required for the optimal expression of certain 
selenoproteins. There was a good correlation between the affinity of nucleolin 
for a SECIS and its effect on selenoprotein expression. As selenoprotein 
transcript levels and localization did not change in siRNA-treated cells, our 
results suggest that nucleolin selectively enhances the expression of a subset 
of selenoproteins at the translational level.