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2021 年度 実施状況報告書

Studying the dynamics of a novel small RNA (tiRNA) generation in glioma; possible new therapy

研究課題

研究課題/領域番号 20K16323
研究機関東北大学

研究代表者

Rashad Sherif  東北大学, 医学系研究科, 助教 (00824088)

研究期間 (年度) 2020-04-01 – 2023-03-31
キーワードGlioma / Chemotherapy / tRNA / Cell Stress
研究実績の概要

1) To understand the links between tRNA and Glioma, ALKBH1 overexpression was performed in glioma cell line. Alkbh1 is a tRNA demethylase that enhances tRNA cleavage. Alkbh1 overexpression enhanced glioma invasion, stemness, and resistance to oxidative stress. Alkbh1 achieved its activity via tRNA demethylation, protein translation repression, and translational shifts. Furthermore, Alkbh1 protected glioma cells against ferroptosis. 2) m7G modification was analyzed in glioma cells. Loss of m7G via WDR4 knockdown led to inhibition of proliferation and invasion and induction of stemness. 3) Conducted a study using human surgical glioblastoma samples to analyze tRNA derived small RNA landscape using small RNA sequencing. Data analysis is in progress. 4) Conducted a study on the mechanisms of tiRNA generation during oxidative stress. Identified stress-specific signatures that impact tRNA cleavage in different forms of stress such as mitochondrial stress and endoplasmic reticulum stress. Identified impact of tRNA cleavage on protein translation using ribosome profiling and bioinformatics analysis.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

Several tRNA methylation modifications were discovered to impact glioma pathophysiology. Currently, shRNA and CRISPR knockout based approached are being used to probe the function of these modifications in glioma and their impact on tRNA cleavage and translation.

今後の研究の推進方策

Work will be continued on m1A modifications their responsible enzyme, Alkbh1, as well as on m7G modifications and WDR4 enzyme in glioma. Animal experiments are planned to understand the impact of tRNA methylation on glioma microenvironment and immune responses.

  • 研究成果

    (3件)

すべて 2021

すべて 雑誌論文 (3件)

  • [雑誌論文] The cell and stress‐specific canonical and noncanonical tRNA cleavage2021

    • 著者名/発表者名
      Sherif Rashad, Teiji Tominaga, Kuniyasu Niizuma
    • 雑誌名

      Journal of Cellular Physiology

      巻: 236 ページ: 3710–3724

    • DOI

      10.1002/jcp.30107

  • [雑誌論文] Mature Neurons’ sensitivity to oxidative stress is epigenetically programmed by alternative splicing and mRNA stability2021

    • 著者名/発表者名
      Yuan Zhou, Sherif Rashad, Teiji Tominaga, Kuniyasu Niizuma
    • 雑誌名

      Biorxiv preprint

      巻: 00 ページ: 00

    • DOI

      10.1101/2021.12.25.472549

  • [雑誌論文] Epigenetic regulation of translation repression in ferroptosis, and a role of Alternative splicing and tRNA methylation2021

    • 著者名/発表者名
      Sherif Rashad, Daisuke Saigusa, Yuan Zhou, Liyin Zhang, Teiji Tominaga, Kuniyasu Niizuma
    • 雑誌名

      Biorxiv preprint

      巻: 00 ページ: 00

    • DOI

      10.1101/2021.11.10.468143

URL: 

公開日: 2022-12-28  

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