Original article

BioMedicine

, 5:10

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

P-coumaric acid regulates exon 12 splicing of the ATP7B gene by modulating hnRNP A1 protein expressions

  • Ying-Ju LinAffiliated withGenetic Center, Department of Medical Research, China Medical University HospitalSchool of Chinese Medicine, China Medical University
  • , Tsung-Jung HoAffiliated withSchool of Chinese Medicine, China Medical UniversityDivision of Chinese Medicine, China Medical University Beigang HospitalDivision of Chinese Medicine, Tainan Manicipal An-Nan Hospital -China Medical University
  • , Ting-Hsu LinAffiliated withGenetic Center, Department of Medical Research, China Medical University Hospital
  • , Wei-Yi HsuAffiliated withGenetic Center, Department of Medical Research, China Medical University Hospital
  • , Shao-Mei HuangAffiliated withGenetic Center, Department of Medical Research, China Medical University Hospital
  • , Chiu-Chu LiaoAffiliated withGenetic Center, Department of Medical Research, China Medical University Hospital
  • , Chih-Ho LaiAffiliated withDepartment of Microbiology, School of Medicine, China Medical University
  • , Xiang LiuAffiliated withNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda
  • , Hsinyi TsangAffiliated withNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda
    • , Chien-Chen LaiAffiliated withInstitute of Molecular Biology, National Chung Hsing University
    • , Fuu-Jen TsaiAffiliated withGenetic Center, Department of Medical Research, China Medical University HospitalSchool of Chinese Medicine, China Medical UniversityDepartment of Biotechnology, Asia University

Abstract

Background: Wilson’s disease (WD) is a genetic disorder involving the metabolism of copper. WD patients exhibit a wide range of disease phenotypes, including Kayser-Fleischer rings in the cornea, predominant progressive hepatic disease, neurological diseases, and/or psychiatric illnesses, among others. Patients with exon12 mutations of the ATP7B gene have progressive hepatic disease. An ATP7B gene that lacks exon12 retains 80% of its copper transport activities, suggesting that alternative splicing of ATP7B gene may provide alternative therapeutic ways for patients with inherited sequence variants and mutations of this gene. Purpose: We aimed to search for possible Chinese herbs and related compounds for modulating ATP7B premRNA splicing.

Methods: We used an ATP7B exon11-12-13 mini-gene vector as a model and screened 18 Chinese herbal extracts and four compounds from Schizonepeta to determine their effects on ATP7B pre-mRNA splicing in vitro.

Results: We found that Schizonepeta demonstrated the greatest potential for alternative splicing activity. Specifically, we found that p-coumaric acid from this herb enhanced ATP7B exon12 exclusion through the down-regulation of heterogeneous ribonucleoprotein (hnRNP) A1 protein expressions.

Conclusion: These results suggest that there are herbs or herb-related compounds that could modify the alternative splicing of the ATP7B gene via a mechanism that regulates pre-mRNA splicing.

Keywords:

Wilson’s disease Schizonepeta p-coumaric acid hnRNP A1 Alternative splicing