Global disorder of splicing caused by oncogene product HMGA1

2015 Fiscal Year Final Research Report

• Project/Area Number: 24310161
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Living organism molecular science
• 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(Kenkyū-buntansha): KATAYAMA Tai-ichi 大阪大学, 連合小児発達学研究科, 教授 (80333459) ; MUTOH Yutaka 武蔵野大学, 薬学部 薬学科, 教授 (30192769)
• Co-Investigator(Renkei-kenkyūsha): NAMEKI Kanako (桑迫 香奈子) 武蔵野大学, 薬学部 薬学科, 講師 (10568736) ; OHE Kenji 福岡大学, 薬学部 臨床薬物治療学, 准教授 (30419527)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 遺伝子発現 / スプライシング / HMGA1 / Presenillin-2 / アルツハイマー病 / 癌

Outline of Final Research Achievements

We previously elucidated the mechanism of aberrant splicing of the presenilin-2 pre-mRNA, specifically observed in the patients of sporadic Alzheimer’s disease. In this study, we tried to solve the functional structure, HMGA1α-U1 snRNP-target RNA complex. The interactions were analyzed by a highly sensitive isothermal titration calorimeter and ES-mass spectrometer. Intriguingly, we found that HMGA1α is also involved in the specific alternative splicing of Estrogen receptor α (ERα) pre-mRNA and AIDS virus (HIV-1) transcript. The shared mechanism was that the HMGA1α binds to the target sequence and interferes with the adjacent 5′ splice site via aberrant binding of U1 snRNP, the 5′ splice site recognition factor.

Free Research Field

分子生物学