Elucidating the role of tRNA epitranscriptome in Glioma pathology and development of novel therapies

2023 Fiscal Year Annual Research Report

• Project/Area Number: 23H02741
• Allocation Type: Single-year Grants
• Research Institution: Tohoku University
• Principal Investigator: Rashad Sherif 東北大学, 医工学研究科, 准教授 (00824088)
• Co-Investigator(Kenkyū-buntansha): 遠藤 俊毅 東北医科薬科大学, 医学部, 教授 (00535370) ; 七谷 圭 東北大学, 未来型医療創成センター, 助教 (00547333) ; 新妻 邦泰 東北大学, 医工学研究科, 教授 (10643330) ; 金森 政之 東北大学, 医学系研究科, 准教授 (60420022)
• Project Period (FY): 2023-04-01 – 2026-03-31
• Keywords: tRNA / Glioma / Codon bias / mRNA translation

Outline of Annual Research Achievements

During the past year, I was able to finish 2 manuscripts related to tRNA modifications and their potential role. The manuscripts were published as preprints and currently are under review (Al-Mesitef et al, 2024; Rashad et al, 2024). I also presented the preliminary results of my work in the RNA society meeting 2023 in Singapore and The American Society for Cell Biology 2023 in Boston. I was also able to improve the mass spectrometry method and analyze patient derived glioma samples that led to major discovery in terms of tRNA modifications and glioma that is currently being explored.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Analysis of patient drived glioma samples revealed many tRNA modifications of interest that will be systematically targeted in the next stage. The progress in the analysis of ALKBH1 in glioma is going smoothly and a manuscript is expected to be prepared this year. Structural studies are underway.

Strategy for Future Research Activity

The orignal plan will continue with expansion to a number of tRNA modifications based on the analysis conducted.

Research Products

• [Journal Article] Translational response to mitochondrial stresses is orchestrated by tRNA modifications (2024)
  • Author(s): Sherif Rashad, Shadi Al-Mesitef, Abdulrahman Mousa, Yuan Zhou, Daisuke Ando, Guangxin Sun, Tomoko Fukuuchi, Yuko Iwasaki, Jingdong Xiang, Shane R Byrne, Jingjing Sun, Masamitsu Maekawa, Daisuke Saigusa, Thomas J Begley, Peter C Dedon, Kuniyasu Niizuma
  • Journal Title: Biorxiv preprint Volume: 00 Pages: 00
  • DOI: 10.1101/2024.02.14.580389
  • Open Access / Int'l Joint Research
• [Journal Article] Angiogenin regulates mitochondrial stress and function via tRNA-derived fragments generation and impacting tRNA modifications (2024)
  • Author(s): Shadi Al-Mesitef, Keita Tominaga, Abdulrahman Mousa, Thomas J Begley, Peter C Dedon, Sherif Rashad, Kuniyasu Niizuma
  • Journal Title: Biorxiv preprint Volume: 00 Pages: 00
  • DOI: 10.1101/2024.02.13.580206
  • Open Access / Int'l Joint Research
• [Journal Article] Mammalian tissue specific translation regulation; role of tRNA epitranscriptome in regulating codon optimality patterns across tissues (2023)
  • Author(s): Daisuke Ando, Sherif Rashad, Thomas J Begley, Hidenori Endo, Masashi Aoki, Peter C Dedon, Kuniyasu Niizuma
  • Journal Title: Biorxiv preprint Volume: 00 Pages: 00
  • DOI: 10.1101/2023.10.24.563884
  • Open Access / Int'l Joint Research
• [Presentation] Translational regulation of mitochondrial stress response via the tRNA epitranscriptome. (2023)
  • Author(s): Sherif Rashad
  • Organizer: RNA 2023 meeting Singapore (International RNA society meeting)
  • Int'l Joint Research
• [Presentation] Neuronal sensitivity to oxidative stress is epi- and post-transcriptionally regulated (2023)
  • Author(s): Sherif Rashad
  • Organizer: Brain Japan 2023 (Japan society for cerebral blood flow and metabolism meeting)
• [Presentation] tRNA Queuosine modifications regulate translationalresponse to mitochondrial stress (2023)
  • Author(s): Sherif Rashad , Shadi Al-Mesitef , Abdulrahman Mousa , Daisuke Saigusa , Thomas Begley , Peter Dedon , Kuniyasu Niizuma
  • Organizer: Cell bio 2023 (American society for cell biology meeting)
  • Int'l Joint Research
• [Presentation] Ribosome collisions is targetable vulnerability inglioma during ferroptosis exposure (2023)
  • Author(s): Tianxiang Zhang, Sherif Rashad , Kuniyasu Niizuma;
  • Organizer: Cell bio 2023 (American society for cell biology meeting)
  • Int'l Joint Research
• [Presentation] SAMD4A regulates neuronal differentiation andsensitivity to oxidative stress via altering mRNA stability (2023)
  • Author(s): Yuan Zhou, Sherif Rashad , Kuniyasu Niizuma;
  • Organizer: Cell bio 2023 (American society for cell biology meeting)
  • Int'l Joint Research
• [Presentation] Neuronal sensitivity to oxidative stress is an epi and post transcriptional consequence to neuronal differentiation. (2023)
  • Author(s): Yuan Zhou, Sherif Rashad , Kuniyasu Niizuma;
  • Organizer: RNA Japan meeting 2023