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2023 Fiscal Year Final Research Report

Computational Prediction and Experimental Validation of the Regulatory Mechanisms of Functional Peptides Encoded in Genomic Junk Regions

Research Project

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Project/Area Number 21K12107
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 62010:Life, health and medical informatics-related
Research InstitutionKanazawa University

Principal Investigator

Shuichi Fukuyoshi  金沢大学, 薬学系, 講師 (10456410)

Co-Investigator(Kenkyū-buntansha) 伊藤 素行  千葉大学, 大学院薬学研究院, 教授 (20377906)
清水 謙多郎  東京大学, 大学院農学生命科学研究科(農学部), 教授 (80178970)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywordsリボソーム / uORF / シミュレーション / ドッキング / 翻訳アレスト
Outline of Final Research Achievements

In the genome, only 2% of sequences code for proteins, while the remaining non-coding regions were previously considered meaningless junk regions. However, with recent advancements in molecular biology, comprehensive analyses of which sequences in the genome are being translated have revealed that non-coding regions, previously thought to be junk, are also being translated and are believed to regulate protein synthesis. In this study, we focused on the translated regions, called uORFs, located in the non-coding regions upstream of the protein-coding regions on mRNA. To elucidate the interactions between the peptide chains generated by translation and the inner walls of the ribosome, we conducted docking simulations.

Free Research Field

計算科学

Academic Significance and Societal Importance of the Research Achievements

uORFから翻訳されたペプチド鎖にはリボソーム内で停滞することで翻訳を停止させるシス作用と、別のタンパク質のリガンドとして働くトランス作用がある。リボソーム内でのペプチド鎖の挙動の解明は、ヒトの遺伝子に存在するuORFの翻訳や作用メカニズムを推定できるだけでなく、シス・トランス作用を持つ小さなペプチド配列を設計することも可能になる。シス・トランスに働くuORFのどちらも、低分子化合物によって制御されると考えられるため、本研究は翻訳制御を阻害する新しい薬の開発につながる可能性がある。

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Published: 2025-01-30  

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