非酵素結合による短いオリゴマーからリボ酵素リゲーズの組成

Lijun Zhou^1,2, Derek K O'Flaherty^1,2, Jack W Szostak^1,2,3

¹Howard Hughes Medical Institute, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, United States.

Journal of the American Chemical Society

|August 22, 2020

まとめ

研究者は短いオリゴヌクレオチドから活性リボ酵素を作る方法を開発しましたこれは初期の遺伝物質化学の課題を克服し,非酵素から酵素結合への移行を示しています.

科学分野:

生命の起源
RNA世界仮説
化学生物学

背景:

原始的な遺伝物質の化学的性質の理解は限られています
オリゴヌクレオチドの効率的な非酵素的な模板複製は,触媒化のために困難です.
短いオリゴヌクレオチドから機能的なリボ酵素を組み立てることは,潜在的な解決策です.

研究の目的:

非酵素的なテンプレート複製の低効率を回避するために.
テンプレート結合による活性リボ酵素の組み立て方法を探求する.
組み立てられたリボ酵素のスプリントオリゴヌクレオチド阻害に対処する.

主な方法:

ショートオリゴヌクレオチドのテンプレート結合によって組み立てられた機能的リボ酵素.
リボ酵素の阻害を最小限に抑えながら効率的な結合を可能にするために設計されたスプリントオリゴヌクレオチド.
3つのスプリントデザインを調査した.DNAスプリント,G:U振動ペア,GからI (イノシン) 置換.

主要な成果:

テンプレート結合で活性リボ酵素を組み立てました
DNAスプリント,G:U振動ペア,GからIの置換がスプリント阻害を効果的に減少させることを実証しました.
テストされたスプリント設計で活性リボ酵素連鎖の効率的な組み立てを達成しました.

結論:

原始的な遺伝物質の組み立てには,非酵素結合から酵素結合への移行が可能である.
補完性オリゴヌクレオチド (スプリント) の慎重な設計は,触媒活性抑制を避けるために極めて重要です.
この研究は,早期のRNAベースの触媒と複製の実現可能性に関する洞察を提供します.

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