Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots
Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots
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DOI：
10.1073/pnas.1219988110
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发表时间：
2013-04-02
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：
Hajdin, Christine E.;Bellaousov, Stanislav;Weeks, Kevin M.
当一个环中的核苷酸与封闭该环的螺旋外部区域配对时，RNA中就会形成假结。假结在RNA中相对罕见，但在大型催化RNA、核糖开关以及病毒的调控元件中具有关键功能的基序中高度富集。RNA结构预测算法通常不考虑假结。当纳入假结时，这些配对很难精确建模，特别是在大型RNA中，因为允许这种结构会极大地增加可能的错误折叠数量，而且很难在折叠空间中搜索最优结构。我们开发了一种简洁的二级结构建模方法，它结合了SHAPE（通过引物延伸分析的选择性2'-羟基酰化）实验化学探测信息以及一个简单但稳健的单个假结形成的熵成本能量模型。利用动态规划算法通过迭代优化来预测结构。这种融合了实验和热力学能量函数预测了一组21种已知结构、大小从34到530个核苷酸的具有挑战性的RNA的二级结构和假结。平均而言，93%的已知碱基对被预测出来，并且在折叠良好的RNA中的所有假结都被识别出来。
A pseudoknot forms in an RNA when nucleotides in a loop pair with a region outside the helices that close the loop. Pseudoknots occur relatively rarely in RNA but are highly overrepresented in functionally critical motifs in large catalytic RNAs, in riboswitches, and in regulatory elements of viruses. Pseudoknots are usually excluded from RNA structure prediction algorithms. When included, these pairings are difficult to model accurately, especially in large RNAs, because allowing this structure dramatically increases the number of possible incorrect folds and because it is difficult to search the fold space for an optimal structure. We have developed a concise secondary structure modeling approach that combines SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) experimental chemical probing information and a simple, but robust, energy model for the entropic cost of single pseudoknot formation. Structures are predicted with iterative refinement, using a dynamic programming algorithm. This melded experimental and thermodynamic energy function predicted the secondary structures and the pseudoknots for a set of 21 challenging RNAs of known structure ranging in size from 34 to 530 nt. On average, 93% of known base pairs were predicted, and all pseudoknots in well-folded RNAs were identified.