In mammalian somatic cells, the post-transcriptional control of cytokine or proto-oneogene 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., (c) 2006 Elsevier Inc. All rights reserved.