Investigation of the global effect and the mechanism of cancer specific mature mRNA re-splicing

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430124
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Fujita Health University
• Principal Investigator: Kameyama Toshiki 藤田保健衛生大学, 総合医科学研究所, 助教 (60298544)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: がん / 異常スプライシング / RNA結合タンパク質 / siRNAライブラリー

Outline of Final Research Achievements

We have discovered cancer-specific mRNA re-splicing that occurs on mature spliced mRNA and generates aberrant transcripts/proteins. The control of the re-splicing could be promoted by unknown activator upregulated and/or repressor downregulated in cancer cells.
Recent striking findings represent a breakthrough in the study of mRNA re-splicing. (1) TSG101 delta protein, generated via re-splicing of TSG101, enhances TSG101-stimulated cell proliferation and tumor growth. (2) mRNA re-splicing is repressed by the expression of TP53 often induced by cellular stress, (3) We have identified a repressor candidate of mRNA re-splicing by screening of siRNA library (156 kinds of RNA-binding proteins). Since the identified repressor is a known tumor suppressor, we postulate that global prevention of aberrant mRNA re-splicing, maintaining fidelity of splicing, is critical for the consequent tumor suppression. To prove this hypothesis is underway.

Free Research Field

分子細胞生物学