In vitro RNA random pools are not structurally diverse: A computational analysis
In vitro RNA random pools are not structurally diverse: A computational analysis
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DOI：
10.1261/rna.7271405
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发表时间：
2005-06-01
期刊：
影响因子：
4.5
通讯作者：
Schilick, T
中科院分区：
文献类型：
--
作者：
Gevertz, J;Gan, HH;Schilick, T
从大型随机序列库中体外选择功能性 RNA 已导致许多配体结合和催化 RNA 的鉴定。然而，随机池中的结构多样性尚不清楚。这种理解是设计序列池的先决条件，以增加通过体外选择技术发现复杂功能RNA的可能性。为了实现这一目标，我们通过计算机生成了五个长度高达 100 nt 的随机 RNA 序列池来模拟实验，并使用源自图论技术的一组可能的 RNA 树结构来表征相关二级结构基序的分布。我们的结果表明，这样的随机池非常有利于简单的拓扑结构：例如，线性茎环和低分支基序比具有高阶连接的复杂结构更受青睐，正如已知适体所证实的那样。此外，我们量化了结构复杂性随序列长度的增加，并报告了每个池的树基序的主要类别（以顶点数为特征）。这些分析不仅表明随机池不会导致可能的 RNA 二级拓扑的均匀分布；他们指出了设计具有相同丰度的特定简单和复杂结构池的途径，以扩大通过体外选择发现的功能性RNA的范围。具体来说，识别具有 x 个茎的结构的最佳 RNA 序列池长度是 20x。
In vitro selection of functional RNAs from large random sequence pools has led to the identification of many ligand-binding and catalytic RNAs. However, the structural diversity in random pools is not well understood. Such an understanding is a prerequisite for designing sequence pools to increase the probability of finding complex functional RNA by in vitro selection techniques. Toward this goal, we have generated by computer five random pools of RNA sequences of length up to 100 nt to mimic experiments and characterized the distribution of associated secondary structural motifs using sets of possible RNA tree structures derived from graph theory techniques. Our results show that such random pools heavily favor simple topological structures: For example, linear stem-loop and low-branching motifs are favored rather than complex structures with high-order junctions, as confirmed by known aptamers. Moreover, we quantify the rise of structural complexity with sequence length and report the dominant class of tree motifs (characterized by vertex number) for each pool. These analyses show not only that random pools do not lead to a uniform distribution of possible RNA secondary topologies; they point to avenues for designing pools with specific simple and complex structures in equal abundance in the goal of broadening the range of functional RNAs discovered by in vitro selection. Specifically, the optimal RNA sequence pool length to identify a structure with x stems is 20x.