Alternative splicing involved in toxicity by environmental chemicals

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670068
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Tokushima Bunri University
• Principal Investigator: SUMI Daigo 徳島文理大学, 薬学部, 准教授 (30400683)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: スプライシング / 環境化学物質 / mRNA

Outline of Final Research Achievements

In this study, we examined whether environmental chemicals and oxidative stress trigger the alternative splicing. Firstly, we measured reactive oxygen species trigger the alternative splicing of AS3MT gene. After exposure of HepG2 cells to hydrogen peroxide (H2O2), we detected a novel splice form of AS3MT mRNA, which are exon 3 to 9 skipping (Δ3-9). Although several factors such as serine-arginine rich (SR) and heterogeneous nuclear ribonucleoprotein (hnRNP) are found as candidate splice factors that can bind to the exons of AS3MT gene, we detected that the levels of SRp40 protein was decreased on H2O2 exposure through ubiquitin-proteasome pathway. In addition, we detected the deletion of arsenic methytransferase activity on this splicing form.
We found that alternative splicing is induced in cells exposed to arsenite and paraquat, which is bipyridinium herbicide as environmental chemicals. Currently, we are examining for more information.

Free Research Field

環境分子毒性学