Search for the cause of proteomic disorder without genomic mutations in the global mis-regulation of splicing

2015 Fiscal Year Final Research Report

• Project/Area Number: 25640081
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnostics
• Research Institution: Fujita Health University
• Principal Investigator: MAYEDA Akila 藤田保健衛生大学, 総合医科学研究所, 教授 (50212204)
• Co-Investigator(Renkei-kenkyūsha): KAMEYAMA Toshiki 藤田保健衛生大学, 総合医科学研究所, 助教 (60298544) ; SHIROKI Ryoichi 藤田保健衛生大学医学部, 腎泌尿器外科学, 教授 (70226330) ; SUGIOKA Atsushi 藤田保健衛生大学医学部, 肝脾外科学, 教授 (20171150) ; UTSUMI Toshiaki 藤田保健衛生大学医学部, 乳腺外科学, 教授 (10176711)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 遺伝子発現調節 / スプライシング / mRNA / 品質管理機構 / 癌

Outline of Final Research Achievements

We discovered re-splicing event in cancer cells that occurs on mature spliced mRNA and generates aberrant mRNAs. This ‘mRNA re-splicing’ event not only explains a global splicing mis-regulation in cancer, but also implies an mRNA-quality control mechanism that prevents deleterious extra re-splicing in normal cells. Therefore, we tried to search for the regulation factors of the mRNA re-splicing. Intriguingly, tumor suppressor p53 factor prevented mRNA re-splicing, while it was promoted by the epithelial-mesenchymal transition factor TGF-β. Our results suggest considerable implication of the mRNA re-splicing event in the progression and suppression of cancer.

Free Research Field

分子生物学