Regulation of cIAP1 mRNA Stability Through Its 3’ UTR by the RNA-Binding Protein HuR

Abstract

The RNA-binding protein HuR is involved in numerous aspects of the RNA life-cycle. It is known for its ability to stabilize AU-Rich Element (ARE)-containing transcripts in the cytoplasm. The transcript of cIAP1, an important protein involved both in the regulation of apoptosis and NF-κB signaling, contains four such AREs, raising the question of whether HuR can modulate the stability of cIAP1 mRNA. First, using C2C12 cells, we observed a positive correlation between cIAP1 mRNA levels and HuR cytoplasmic localization. We then show that knockdown of HuR in U2OS cells results in a decrease in steady-state cIAP1 mRNA levels through destabilization of the cIAP1 mRNA. Furthermore, we are able to show in vitro that HuR binds directly to the second of the four AREs in the 3’ UTR. The direct link between the binding of HuR to the second ARE and its effect on cIAP1 mRNA stability remains to be shown.