Charge density of divalent metal cations determines RNA stability

Charge density of divalent metal cations determines RNA stability
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DOI:
10.1021/ja068027r
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发表时间:
2007-03-07
影响因子:
15
通讯作者:
Woodson, Sarah A.
Woodson, Sarah A.
中科院分区:
化学1区
文献类型:
--
作者:
Koculi, Eda;Hyeon, Changbong;Woodson, Sarah A.

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核糖核酸分子对反离子的性质极为敏感。在二价IIA金属阳离子存在下,用非变性凝胶电泳法测定四膜虫核酶的折叠平衡。折叠核酶的稳定性随着阳离子的电荷密度(Zeta)的增加而增加。当通过尿素变性测量RNA在小金属阳离子和大金属阳离子中折叠的自由能时,也发现了类似的标度。聚电解质的布朗动力学模拟表明,在没有特定位置的金属络合的情况下,实验观察可以用非特定的离子-RNA相互作用来解释。实验和模拟结果表明,RNA的稳定性在很大程度上取决于反离子电荷和凝聚阳离子的堆积效率,后者取决于阳离子的排除体积。
RNA molecules are exquisitely sensitive to the properties of counterions. The folding equilibrium of the Tetrahymena ribozyme is measured by nondenaturing gel electrophoresis in the presence of divalent group IIA metal cations. The stability of the folded ribozyme increases with the charge density (zeta) of the cation. Similar scaling is found when the free energy of the RNA folded in small and large metal cations is measured by urea denaturation. Brownian dynamics simulations of a polyelectrolyte show that the experimental observations can be explained by nonspecific ion-RNA interactions in the absence of site-specific metal chelation. The experimental and simulation results establish that RNA stability is largely determined by a combination of counterion charge and the packing efficiency of condensed cations that depends on the excluded volume of the cations.