Protein expression is increased by a class III AU-rich element and tethered CUG-BP1

In mammalian somatic cells, the post-transcriptional control of cytokine or proto-oncogene expression is often achieved by factors binding to sequence elements in the 3′ untranslated region (3′UTR). The most studied are the AU-rich elements (ARE) that have been divided into three classes. Here, we show that in mammalian cells, the presence of the class III c-jun ARE in the 3′UTR of a reporter mRNA enhanced reporter protein expression. In contrast, the presence of a class II ARE in the 3′UTR decreased reporter protein expression. CUG-BP1/CELF1 is able to bind c-jun ARE. Protein expression was enhanced similarly to what was observed for c-jun ARE when the reporter mRNA contained a synthetic CUG-BP1/CELF1-binding site, or when this protein was tethered to the 3′UTR of a reporter mRNA. These results reveal an unexpected complexity of ARE-mediated post-transcriptional regulations, and indicate a function for CUG-BP1/CELF1 in class III ARE directed regulations.