P-coumaric Acid Regulates Exon 12 Splicing of the ATP7B Gene by Modulating HnRNP A1 Protein Expressions

Overview

Journal Biomedicine (Taipei)

Specialty Biomedical Engineering

Date 2015 Jun 7

PMID 26048696

Citations 25

Authors

Ying-Ju Lin

Tsung-Jung Ho

Ting-Hsu Lin

Wei-Yi Hsu

Shao-Mei Huang

Chiu-Chu Liao

Chih-Ho Lai

Xiang Liu

Hsinyi Tsang

Chien-Chen Lai

Fuu-Jen Tsai

Affiliations

Soon will be listed here.

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.

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