The mammalian gene ZNF268 is regulated by hUpf1

Nonsense-mediated mRNA decay (NMD), also called RNA surveillance, is a process that degrades mRNAs with premature translation termination codons. In Saccharomyces cerevisiae , it has also been shown that NMD can regulate gene expression at the transcriptional level. To date, there has been no example where promoters are regulated by the NMD path-way in higher eukaryotes. Taking advantage of our previous research on ZNF268 transcription control, we studied the relationship between the ZNF268 promoter and the NMD pathway. We showed by transient transfection that the ZNF268 promoter activity was influenced by hUpf1, not hSmg6, in HeLa cells. This result was confirmed by the analysis of the steady state mRNA of ZNF268 after depletion of endogenous hUpf1 or hSmg6 in HeLa cells. Direct mutational analysis revealed that the C/EBP site in the promoter region is important for hUpf1 function on ZNF268 promoter. Together our results demonstrated that the mammalian gene ZNF268 is regulated by hUpf1 via its promoter.