Correlating SHAPE signatures with three-dimensional RNA structures
Correlating SHAPE signatures with three-dimensional RNA structures
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DOI：
10.1261/rna.2640111
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发表时间：
2011-09-01
期刊：
影响因子：
4.5
通讯作者：
Shapiro, Bruce A.
中科院分区：
文献类型：
--
作者：
Bindewald, Eckart;Wendeler, Michaela;Shapiro, Bruce A.
引物延伸法（SHAPE）是一种简便的定量分析RNA二级结构的方法。一般来说，低SHAPE信号值表示沃森-克里克碱基配对，高值表示RNA结构内的单链位置。然而，SHAPE信号与结构性质如非沃森-克里克碱基配对或堆叠的关系迄今尚未得到彻底研究。在这里，我们提出了几个RNA与公布的三维结构进行SHAPE实验的结果。这种策略使我们能够分析结果的化学反应性和相应核苷酸的结构特性之间的相关性，如不同类型的碱基配对，堆叠和磷酸骨架相互作用。我们发现RNA SHAPE信号与顺式沃森-克里克/沃森-克里克碱基配对密切相关，并且在很大程度上不依赖于除堆叠外的其他结构特性。我们随后生成概率模型，估计具有给定SHAPE评分的残基参与碱基配对的可能性。我们发现，考虑到相邻残基的SHAPE分数的几种模型在预测碱基配对方面比单个SHAPE分数表现更好。这强调了SHAPE的上下文敏感性，并为改进RNA对化学修饰的反应的解释提供了一个框架。
Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) is a facile technique for quantitative analysis of RNA secondary structure. In general, low SHAPE signal values indicate Watson-Crick base-pairing, and high values indicate positions that are single-stranded within the RNA structure. However, the relationship of SHAPE signals to structural properties such as non-Watson-Crick base-pairing or stacking has thus far not been thoroughly investigated. Here, we present results of SHAPE experiments performed on several RNAs with published three-dimensional structures. This strategy allows us to analyze the results in terms of correlations between chemical reactivities and structural properties of the respective nucleotide, such as different types of base-pairing, stacking, and phosphate-backbone interactions. We find that the RNA SHAPE signal is strongly correlated with cis-Watson-Crick/Watson-Crick base-pairing and is to a remarkable degree not dependent on other structural properties with the exception of stacking. We subsequently generated probabilistic models that estimate the likelihood that a residue with a given SHAPE score participates in base-pairing. We show that several models that take SHAPE scores of adjacent residues into account perform better in predicting base-pairing compared with individual SHAPE scores. This underscores the context sensitivity of SHAPE and provides a framework for an improved interpretation of the response of RNA to chemical modification.