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一个交叉的RNA聚合酶 ribozyme
Jonathan T Sczepanski1, Gerald F Joyce1
1Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|November 4, 2014
概括
研究人员开发了一种新型的交叉性RNA聚合酶,可以克服性抑制,使D-和L-RNA分子的复制成为可能. 这一突破解决了理解基于RNA的生命起源的关键挑战.
科学领域:
- 生命的起源研究 生命的起源研究
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 活性单核酸的模板导向聚合被对立的反反体抑制,这对早期基于RNA的生命构成了挑战.
- 能够催化RNA聚合的RNA酶 (核糖酶) 的出现对RNA复制和进化至关重要.
- 以前假设早期的RNA聚合酶及其基质具有相同的奇拉性 (手性).
研究的目的:
- 研究交叉性RNA复制的可能性,其中一只手的RNA酶可以聚合相反手的基质.
- 通过体外进化来设计一个功能性的交叉性RNA聚合酶.
- 为了证明基于RNA的生命可以从具有破碎的合对称性的系统中出现.
主要方法:
- 实验室进化被采用,从随机序列RNA分子的多样化群体开始.
- 选择压力被应用于识别可催化非本地性质基质聚合的RNA序列.
- 进化RNA酶的催化活性和基质特异性的特征.
主要成果:
- 一种83核酸D-RNA酶被开发出来,可以有效地催化L-RNA基质的模板聚合.
- 还开发了一种补充的L-RNA酶,证明了与D-RNA基质具有相似的交叉性催化活性.
- 基拉尔抑制被规避了,因为进化的酶仅在交叉基拉尔基质 (高达106倍) 上表现出显著的速率加速.
- 交叉性RNA聚合酶证明了合成其自身反体的全长RNA副本的能力.
结论:
- 交叉性RNA聚合酶可以进化,为克服基于RNA的生命起源中的性抑制提供了可信的机制.
- D-和L-RNA复制系统的出现可能同时发生,由交叉性催化剂促进.
- 这一发现支持了这样一个假设:通过化学过程,可以打破奇拉对称性,为RNA进化铺平道路.
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