AU-rich elements (AREs) are RNA-binding domains recognized by certain RBPs, such as Human antigen (Hu) R (HuR), and ARE/poly(U)-binding/degradation factor 1 (AUF1), both implicated in controlling mRNA stability.72,73 AREs are present in the 3′UTR of TNF mRNA and modulate TNF production at post-transcriptional level. Di Marco and colleagues showed that two polymorphisms (GAU and CAU trinucleotide insertions), localized in the 3′UTR of TNF mRNA, affect the binding of RBPs, with consequent reduction in the TNF protein expression a mouse model. Importantly, they showed that the polymorphism reduced HuR binding affinity to the ARE, thereby decreasing the production of TNF protein in macrophages.74
