Abstract:

Berberine (BBR) is a natural small molecule with various pharmacological activities and biological targets. BBR has been shown to inhibit mRNA decay in our previous studies, which is associated with its high binding affinity to the poly-adenine (poly A) tail at the 3′ end of mRNA. However, the exact mechanism remains unknown. In this research, we discovered that deficiency of cytoplasmic poly A binding protein (PABP), which protects mRNA from nucleolytic attack as a poly A-PABP complex, led to the loss of BBR’s effect on mRNA decay inhibition. We also demonstrated using fluorescence spectroscopy, RNA-EMSA (RNA-electrophoretic mobility shift assay) in vitro, and RIP (RNA immunoprecipitation) that BBR could significantly promote PABP binding to poly A. We might conclude that BBR could stabilize mRNA by enhancing the interaction between poly A and PABP. In addition, the HMBC (¹H detected heteronuclear multiple bond correlation) studies demonstrated that BBR could bind to AMP, a monomer of poly A, directly and specifically. Further evidence of molecular docking suggested that BBR might act as a linker to stabilize the poly A-PABP, and elongate the half-life of mRNAs. This demonstrates that BBR might affect protein translation initiation and up-regulate protein expression.

Key words: Berberine, Poly A, PABP, RNA degradation, Pharmacology