Accurate SHAPE-directed RNA structure determination
Accurate SHAPE-directed RNA structure determination
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DOI：
10.1073/pnas.0806929106
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发表时间：
2009-01-06
影响因子：
11.1
通讯作者：
Weeks, Kevin M.
中科院分区：
文献类型：
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作者：
Deigan, Katherine E.;Li, Tian W.;Weeks, Kevin M.
几乎所有的RNA都可以折叠形成广泛的碱基配对二级结构。这些结构中的许多然后调节了基因表达的许多基本要素。推断这些结构-功能关系需要有可能准确地预测RNA二级结构。然而，对于大RNA的RNA二级结构预测，使得单个序列的单个预测结构可靠地代表正确的结构，仍然是一个悬而未决的问题。在这里，我们证明了来自SHAPE实验的定量的核苷酸分辨信息可以被解释为假自由能变化项，并用于高精度地确定RNA二级结构。自由能最小化，通过使用SHAPE伪自由能，结合最近邻参数，预测了脱蛋白的大肠杆菌16S rRNA(>；1300nt)和一组较小的RNA(75-155nt)的二级结构，准确度高达96%-100%，可与通过比较序列分析获得的最佳精确度相媲美。
Almost all RNAs can fold to form extensive base-paired secondary structures. Many of these structures then modulate numerous fundamental elements of gene expression. Deducing these structure-function relationships requires that it be possible to predict RNA secondary structures accurately. However, RNA secondary structure prediction for large RNAs, such that a single predicted structure for a single sequence reliably represents the correct structure, has remained an unsolved problem. Here, we demonstrate that quantitative, nucleotide-resolution information from a SHAPE experiment can be interpreted as a pseudo-free energy change term and used to determine RNA secondary structure with high accuracy. Free energy minimization, by using SHAPE pseudo-free energies, in conjunction with nearest neighbor parameters, predicts the secondary structure of deproteinized Escherichia coli 16S rRNA (> 1,300 nt) and a set of smaller RNAs (75-155 nt) with accuracies of up to 96-100%, which are comparable to the best accuracies achievable by comparative sequence analysis.