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Functional Roles of Chelated Magnesium Ions in RNA Folding and Function
Biochemistry ( IF 2.9 ) Pub Date : 2021-07-28 , DOI: 10.1021/acs.biochem.1c00012
Ryota Yamagami 1, 2 , Jacob P Sieg 1, 2 , Philip C Bevilacqua 1, 2, 3
Affiliation  

RNA regulates myriad cellular events such as transcription, translation, and splicing. To perform these essential functions, RNA often folds into complex tertiary structures in which its negatively charged ribose–phosphate backbone interacts with metal ions. Magnesium, the most abundant divalent metal ion in cells, neutralizes the backbone, thereby playing essential roles in RNA folding and function. This has been known for more than 50 years, and there are now thousands of in vitro studies, most of which have used ≥10 mM free Mg2+ ions to achieve optimal RNA folding and function. In the cell, however, concentrations of free Mg2+ ions are much lower, with most Mg2+ ions chelated by metabolites. In this Perspective, we curate data from a number of sources to provide extensive summaries of cellular concentrations of metabolites that bind Mg2+ and to estimate cellular concentrations of metabolite-chelated Mg2+ species, in the representative prokaryotic and eukaryotic systems Escherichia coli, Saccharomyces cerevisiae, and iBMK cells. Recent research from our lab and others has uncovered the fact that such weakly chelated Mg2+ ions can enhance RNA function, including its thermodynamic stability, chemical stability, and catalysis. We also discuss how metabolite-chelated Mg2+ complexes may have played roles in the origins of life. It is clear from this analysis that bound Mg2+ should not be simply considered non-RNA-interacting and that future RNA research, as well as protein research, could benefit from considering chelated magnesium.

中文翻译:

螯合镁离子在 RNA 折叠和功能中的功能作用

RNA 调节无数细胞事件,例如转录、翻译和剪接。为了执行这些基本功能,RNA 通常折叠成复杂的三级结构,其中带负电荷的核糖-磷酸骨架与金属离子相互作用。镁是细胞中含量最多的二价金属离子,可中和骨架,从而在 RNA 折叠和功能中发挥重要作用。这已为人所知 50 多年,现在有数千项体外研究,其中大多数使用 ≥10 mM 游离 Mg 2+离子来实现最佳 RNA 折叠和功能。然而,在电池中,游离 Mg 2+离子的浓度要低得多,大多数 Mg 2+被代谢物螯合的离子。在这个观点中,我们整理了来自多个来源的数据,以提供与 Mg 2+结合的代谢物的细胞浓度的广泛总结,并估计在代表性的原核和真核系统大肠杆菌中代谢物螯合的 Mg 2+物种的细胞浓度,酿酒酵母和 iBMK 细胞。我们实验室和其他人最近的研究发现,这种弱螯合的 Mg 2+离子可以增强 RNA 的功能,包括其热力学稳定性、化学稳定性和催化作用。我们还讨论了代谢物如何螯合 Mg 2+复合体可能在生命的起源中发挥了作用。从该分析中可以清楚地看出,结合的 Mg 2+不应简单地视为非 RNA 相互作用,未来的 RNA 研究以及蛋白质研究可以从考虑螯合镁中受益。
更新日期:2021-08-10
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