TAT-HuR-HNS3 is a cell penetrating peptide derived from the human antigen R - nucleocytoplasmic shuttling sequence (HuR-HNS) domain. HuR, also known as embryonic lethal abnormal vision-like 1 (ELAVL1) is a well characterized RNA-binding protein that increases the stability of short lived mRNAs which encode proinflammatory mediators. HuR employs its HNS domain to interact with poly(ADP-ribose) polymerase 1 (PARP1), and intervention by TAT-HuR-HNS3 interrupts this interaction, resulting in lower poly-ADP-ribosylation and decreased cytoplasmic distribution of HuR. TAT-HuR-HNS3 also blocks HuR dimerization and promotes argonaute 2-based miRNA induced silencing complex binding. TAT-HuR-HNS3 lowers the mRNA stability of proini,ammatory mediators in TNF-alpha treated epithelial cells and macrophages, and decreases TNF-alpha induced inflammatory responses in animal lung models.
