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Journal of Chinese Pharmaceutical Sciences ›› 2017, Vol. 26 ›› Issue (1): 53-62.DOI: 10.5246/jcps.2017.01.005

• Original articles • Previous Articles     Next Articles

Berberine inhibits mRNA degradation by promoting the interaction between the poly A tail and its binding protein PABP

Zhiyi Yuan1, Xi Lu2, Fan Lei3, Jun Hu2, Yugang Wang2, Yushuang Chai2, Jingfei Jiang2, Huiyu Li2, Dongming Xing2, Lijun Du2*   

  1. 1. College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
    2. MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, Center for Advanced Chinese Medicine Research, School of Life Sciences, Tsinghua University, Beijing 100084, China
    3. School of Pharmacology and Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China 
  • Received:2016-11-15 Revised:2016-12-20 Online:2017-01-22 Published:2016-12-25
  • Contact: Tel.: +86-010-62796270, E-mail: lijundu@mail.tsinghua.edu.cn
  • Supported by:
    National Natural Science Foundation of China (Grant No. 81374006, 81073092 and 90713043).

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

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