人間の40Sリボソームの成熟の最終段階の構造的基礎

Michael Ameismeier¹, Ivo Zemp², Jasmin van den Heuvel^2,3

¹Gene Center Munich, Department of Biochemistry, University of Munich, Munich, Germany.

Nature

|November 19, 2020

まとめ

人間の40Sリボソームの組み立てには,エンドヌクレアースNOB1の活性化を含む最終的な成熟段階が含まれています. 新しい冷凍-EM構造は,RIOK1を明らかにする

科学分野:

分子生物学
細胞生物学
構造生物学

背景:

ユカリオットのリボソーム (40Sと60Sサブユニット) は,200以上の因子を含む複雑なプロセスを経て組み立てられます.
小型のリボソームサブユニットの成熟は,内核酵素NOB1による18S-E前駆体割れでシトソールで頂点に達する.
NOB1の活性化は,そのパートナーであるPNO1によって制御されますが,最終的な成熟段階は不明のままです.

研究の目的:

人間の40Sリボソームサブユニットの最終的な成熟を明らかにする.
NOB1の活性化と生物生成因子の解離のメカニズムを理解する.
末期40S組立に関わる新しい要因を特定する.

主な方法:

人間の40Sサブユニットの5つの冷凍電子顕微鏡 (cryo-EM) 構造.
40Sの末期における組成と形状の変化の分析
rRNA処理とアセンブリファクターリサイクルにおける特定された因子の役割を評価する機能分析.

主要な成果:

RIOK1はPNO1の位移に重要な役割を果たし,NOB1の活性化とその後のrRNAの分裂を可能にします.
2つの新しい因子,EIF1ADとLRRC47が,遅い40S前の粒子に結合することを特定した.
EIF1ADは効率的な組み立て因子リサイクルと18S-E処理に不可欠です.

結論:

人間の40Sリボソームサブユニット形成の最終段階についての詳細なメカニズム的な洞察.
RIOK1,NOB1,EIF1AD,LRRC47は40S後半のバイオゲネシスにおいて重要な役割を果たしている.
ヒトと酵母菌の小さなリボソームサブユニット組成の根本的な違いを示唆している.

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