分子拥挤促进了 ribozyme 催化 RNA 组装
Saurja DasGupta1,2,3, Stephanie Zhang1,4, Jack W Szostak1,2,3,4
1Department of Molecular Biology, Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
ACS central science
|August 28, 2023
概括
分子拥挤使核酶能够在低的条件下发挥作用,这对早期生命至关重要. 这一发现支持了分子拥挤在原始RNA催化和细胞生命起源中的作用.
科学领域:
- 生命起源研究研究生命的起源.
- RNA生物化学与RNA生物化学
- 益生菌化学 益生菌化学
背景情况:
- ribozymes 对于原始生物学是必不可少的,但需要高 (Mg2+) 度的功能.
- 高度的Mg2+可以降解RNA和破坏前生物细胞膜的稳定性,对早期生命构成挑战.
- 现有的细胞环境通过分子拥挤保持低Mg2+ (<1mM) 的 ribozyme 活性.
研究的目的:
- 研究分子拥挤作为一种策略,以使低Mg2+度的 ribozyme 活动.
- 探索支持与生命起源相关的 ribozyme 催化 RNA 组装的条件.
- 为了确定分子拥挤是否可以在变质条件下稳定 ribozyme 功能.
主要方法:
- 在聚乙烯糖醇 (PEG) 的存在下,测试与光化化基质的 ribozyme 催化 RNA 结合.
- 在化条件下 (性pH,尿素) 评估与没有分子拥挤的 ribozyme 活性.
- 评估聚合剂和 prebiotically相关的小分子对RNA催化核三酸盐聚合物的作用.
主要成果:
- 聚乙烯甘醇在低Mg2+的水平上显著增强了 ribozyme 催化 RNA 结合.
- 在性pH和尿素下,分子拥挤保留了 ribozyme 合酶活性.
- 拥挤刺激了RNA催化RNA组合,包括核三酸盐聚合,并被小分子如乙烯基醇,核糖和氨基酸增强.
结论:
- 分子拥挤是一种可行的机制,以支持低Mg2+度的 ribozyme 功能,克服高离子要求的局限性.
- 这一发现对了解原始环境中的基于RNA的催化和早期细胞生命的出现有重大影响.
- 这项研究强调了分子拥挤和简单的有机分子在促进前生物RNA复制和生命起源方面的潜在作用.
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