tRNA epitranscriptome in regulating glioma therapeutic resistance

2022 Fiscal Year Final Research Report

• Project/Area Number: 20KK0338
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Tohoku University
• Principal Investigator: RASHAD Sherif 東北大学, 医学系研究科, 助教 (00824088)
• Project Period (FY): 2020 – 2022
• Keywords: tRNA modifications / Glioma / Ferroptosis / mRNA translation / Codon usage / LC-MS

Outline of Final Research Achievements

During my overseas stay, I was able to learn methods for tRNA modifications analysis using a newly designed LC-MS-based high throughput method. Using this method, I analyzed tRNA modifications in a number of systems we used to study tRNA modifying enzymes. Using CRISPR KO, the impact of tRNA modifications was elucidated in cancer cells, and their impact on mRNA translation was further characterized via Ribosome profiling. In addition, I improved my bioinformatics skills via learning methods to study codon usage and bias and correlate these changes with distinct tRNA modifications signatures. I was able to use these new skills to study the translational impact of ferroptosis and tRNA modifying enzyme ALKBH1 in glioma cells (Rashad et al, Neuroscience, 2022)

Free Research Field

Molecular Neurobiology

Academic Significance and Societal Importance of the Research Achievements

This work will open the doors for discovery of novel targets for cancer therapy that center on mRNA translation control. The first targets have been identified and currently under further studies. Using this system of analysis, novel biomarkers for various diseases can also be elucidated.