The mechanisms regulating the differential selenium (Se)-dependent stability of 
selenoprotein mRNAs are partially characterized. To further study the 
Se-dependent regulation of selenoproteins, we developed a novel chemiluminescent 
reporter to monitor the steady-state mRNA level of an artificial selenoprotein. 
Our reporter is a fusion of the Renilla luciferase gene and of the β-globin 
gene, but contains features required for incorporation of selenocysteine (SEC), 
namely, a UGA-SEC codon and a 3' untranslated region RNA stem loop called a SEC 
incorporation sequence (SECIS). At various levels of Se, the activity of 
reporters containing GPX1 or GPX4 SECIS elements is proportional to the 
steady-state mRNA level of the reporter construct and reflects the level of the 
corresponding endogenous mRNA. In a reporter containing a UGA codon and a 
functional GPX1 SECIS, Se-dependent nonsense-mediated decay (NMD) occurred in 
the cytoplasm, as opposed to the more typical nuclear location. To validate the 
reporter system, we used genetic and pharmacologic approaches to inhibit or 
promote NMD. Modulation of UPF1 by siRNA, overexpression, or by inhibition of 
SMG1 altered NMD in this system. Our reporter is derived from a Renilla 
luciferase reporter gene fused to an intron containing B-globin gene and is 
subject to degradation by NMD when a stop codon is inserted before the second 
intron.