Discovering common stem-loop motifs in unaligned RNA sequences
Discovering common stem-loop motifs in unaligned RNA sequences
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DOI：
10.1093/nar/29.10.2135
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发表时间：
2001-05-15
影响因子：
14.9
通讯作者：
Stormo, GD
中科院分区：
文献类型：
--
作者：
Gorodkin, J;Stricklin, SL;Stormo, GD
基因表达的转录后调控通常是通过与 mRNA 分子中特定序列基序结合的蛋白质来完成的，以影响其翻译或稳定性。基序通常由序列和结构约束的组合组成，这样即使大部分初级序列是可变的，整体结构也得以保留。虽然存在多种方法来发现共调控基因 DNA 序列中的转录调控位点，但由于位置的共变，RNA 基序发现问题要困难得多。我们描述了两种 RNA 结构预测方法（FOLDALIGN 和 COVE）的组合使用，它们可以一起发现和建模未比对序列中的茎环 RNA 基序，例如来自转录后共调控基因的 UTR。我们在两个数据集上评估该方法，一个数据集是末端随机截断的 rRNA 基因部分，因此不可能进行全局比对，另一个数据集是插入随机 UTR 序列的 IRE 类元件的超可变集合。在这两种情况下，组合方法都正确识别了基序，并且在 rRNA 示例中，我们表明它能够确定结构，其中包括凸起和内部环以及可变长度的发夹环。这些自动化结果经过定量评估，发现与精选数据库中包含的结构非常一致，相关系数高达 0.9。基本服务器 Stem-Loop Align SearcH (SLASH) 可以在未对齐的 RNA 序列中执行茎环搜索，可从 http://www.bioinf.au.dk/slash/ 获取。
Post-transcriptional regulation of gene expression is often accomplished by proteins binding to specific sequence motifs in mRNA molecules, to affect their translation or stability. The motifs are often composed of a combination of sequence and structural constraints such that the overall structure is preserved even though much of the primary sequence is variable. While several methods exist to discover transcriptional regulatory sites in the DNA sequences of coregulated genes, the RNA motif discovery problem is much more difficult because of covariation in the positions. We describe the combined use of two approaches for RNA structure prediction, FOLDALIGN and COVE, that together can discover and model stem-loop RNA motifs in unaligned sequences, such as UTRs from posttranscriptionally coregulated genes. We evaluate the method on two datasets, one a section of rRNA genes with randomly truncated ends so that a global alignment is not possible, and the other a hyper-variable collection of IRE-like elements that were inserted into randomized UTR sequences. In both cases the combined method identified the motifs correctly, and in the rRNA example we show that it is capable of determining the structure, which includes bulge and internal loops as well as a variable length hairpin loop. Those automated results are quantitatively evaluated and found to agree closely with structures contained in curated databases, with correlation coefficients up to 0.9. A basic server, Stem-Loop Align SearcH (SLASH), which will perform stem-loop searches in unaligned RNA sequences, is available at http://www.bioinf.au.dk/slash/.