title: P-coumaric acid regulates exon 12 splicing of the ATP7B gene by modulating hnRNP A1 protein expressions.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genetic Center, Department of Medical Research, China Medical University Hospital, No. 2, Yuh-Der Road, 404, Taichung, Taiwan, d0704@mail.cmuh.org.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Lin
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.forename: Ting-Hsu
authors.initials: TH
authors.lastname: Lin
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Hsu
authors.forename: Shao-Mei
authors.initials: SM
authors.lastname: Huang
authors.forename: Chiu-Chu
authors.initials: CC
authors.lastname: Liao
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.forename: Hsinyi
authors.initials: H
authors.lastname: Tsang
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Lai
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai