Sizes of Long RNA Molecules Are Determined by the Branching Patterns of Their Secondary Structures.
Sizes of Long RNA Molecules Are Determined by the Branching Patterns of Their Secondary Structures.
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DOI：
10.1016/j.bpj.2016.10.014
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发表时间：
2016-11-15
影响因子：
3.4
通讯作者：
Tuma, Roman
中科院分区：
文献类型：
--
作者：
Borodavka, Alexander;Singaram, Surendra W.;Stockley, Peter G.;Gelbart, William M.;Ben-Shaul, Avinoam;Tuma, Roman
长RNA分子是所有生命王国基因调控的核心，同时也是RNA病毒的基因组。很少有研究涉及长单链RNA的基本物理性质。具有非重复序列的长RNA通常采用高度分支的二级结构，并且更好地描述为分支聚合物。为了测试分支聚合物模型是否可以估计大RNA的总体大小，我们采用荧光相关光谱法来检查广谱生物学重要RNA的流体动力学半径，从病毒基因组到长的非编码调节RNA。在低离子强度下测得的长RNA的相对大小与两种理论方法预测的相当，这两种理论方法处理与二级结构形成相关的有效分支，一种采用Kramers定理计算回转半径，另一种采用最大阶梯距离的度量。当加入多价阳离子时，发现大多数RNA与其原始的低离子强度尺寸相比被压实。这些结果表明，长RNA分子的大小是由其二级结构的分支模式决定的。我们还通过实验验证了所提出的计算方法，用于估计单链RNA的流体动力学半径，该方法使用通用的RNA结构预测工具，因此可以普遍应用于广泛的长RNA。
Long RNA molecules are at the core of gene regulation across all kingdoms of life, while also serving as genomes in RNA viruses. Few studies have addressed the basic physical properties of long single-stranded RNAs. Long RNAs with nonrepeating sequences usually adopt highly ramified secondary structures and are better described as branched polymers. To test whether a branched polymer model can estimate the overall sizes of large RNAs, we employed fluorescence correlation spectroscopy to examine the hydrodynamic radii of a broad spectrum of biologically important RNAs, ranging from viral genomes to long noncoding regulatory RNAs. The relative sizes of long RNAs measured at low ionic strength correspond well to those predicted by two theoretical approaches that treat the effective branching associated with secondary structure formation—one employing the Kramers theorem for calculating radii of gyration, and the other featuring the metric of maximum ladder distance. Upon addition of multivalent cations, most RNAs are found to be compacted as compared with their original, low ionic-strength sizes. These results suggest that sizes of long RNA molecules are determined by the branching pattern of their secondary structures. We also experimentally validate the proposed computational approaches for estimating hydrodynamic radii of single-stranded RNAs, which use generic RNA structure prediction tools and thus can be universally applied to a wide range of long RNAs.
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