G4:U69塩基対による非同性tRNAへのアラニン誤電の進化的増加

Litao Sun¹, Ana Cristina Gomes², Weiwei He³

¹Department of Cell and Molecular Biology, The Scripps Research Institute , La Jolla, California 92037, United States.

Journal of the American Chemical Society

|September 14, 2016

まとめ

人間の細胞は,特定の酵素 (AlaRS) を通してシステインをアラニンで置き換え,タンパク質の構成要素を変えることができる. この発見はタンパク質の調節のための新しいメカニズムを明らかにしています

科学分野:

分子生物学
生物化学
遺伝学

背景:

アミノアシル-tRNA合成酵素によって制御されるトランスレーションフィデリティは,生物学的正確性にとって極めて重要です.
トランスレーションフィデリティの修正は,規制上の利点を提供することができます.

研究の目的:

ヒトのアラニン-tRNA合成酵素 (AlaRS) が,アラニンを同種でないtRNAに誤結合させる能力を調査する.
このミスチャージ現象の基礎となる構造とシーケンスの決定要因を特定する.

主な方法:

人間とE. coli AlaRSの比較構造分析
バイオケミカルアッセイで,tRNAの誤電を評価する.
tRNA受容体幹における特定の塩基対相互作用の分析.

主要な成果:

人間のAlaRSは,E. coliのAlaRSとは異なり,tRNA^Cysを含むnonalanyl-tRNAにアラニンを誤充電する内在的な能力を有している.
人体細胞のレポータータンパク質にシステインとアラニンの置換が観察され,これはAlaRSの誤電と一致する.
tRNA受容体幹のG4:U69塩基対は,ヒトのAlaRS媒介による誤電に不可欠である.

結論:

人間のAlaRSは拡張されたtRNA特異性を持ち,真核タンパク質の転写後のアラニン置換を可能にします.
AlaRSにおけるこの進化的機能の獲得は,真核生物における規制的役割に役立つのである.
ヒトとバクテリアのAlaRSの主要な配列の違いは,観察された種特有の誤電を説明する.

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