Identification and classification of conserved RNA secondary structures in the human genome.
Identification and classification of conserved RNA secondary structures in the human genome.
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DOI：
10.1371/journal.pcbi.0020033
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发表时间：
2006-04
影响因子：
4.3
通讯作者：
Haussler D
中科院分区：
文献类型：
--
作者：
Pedersen JS;Bejerano G;Siepel A;Rosenbloom K;Lindblad-Toh K;Lander ES;Kent J;Miller W;Haussler D
微RNA和核糖开关等的发现表明，功能性RNA在生物学上比之前预期的更重要，在基因组上也更普遍。我们开发了一种基于系统发育随机上下文无关语法的通用比较基因组学方法，用于识别编码在人类基因组中的功能RNA，并使用它对人类、黑猩猩、小鼠、大鼠、狗、鸡、斑马鱼和河豚基因组进行八向全基因组比对，以寻找高度保守的功能RNA。在一个松散的接受门槛下，这种搜索产生了一组48,479个候选RNA结构。这一筛选发现了大量已知的功能RNA，包括195个miRNAs，62个组蛋白3‘非编码区茎环，以及各种类型的已知遗传记录元件。在得分最高的新预测中有169个新的miRNA候选者，以及新的候选者硒半胱氨酸插入位点，RNA编辑发夹，参与转录自动调节的RNA，以及形成单一或完全未知功能的小功能RNA家族的许多折叠。虽然整个集合中的假阳性率很难估计，而且可能是相当大的，但结果仍然为许多新的人类功能RNA提供了证据，并提出了具体的预测，以便于进一步表征它们。结构功能RNA是细胞的一种多功能成分，包括独立的分子和mRNA转录本的调控元件。最近对功能RNA的许多发现，尤其是miRNAs，表明还有更多的尚未发现。传统上，由于缺乏强序列信号，功能RNA的计算鉴定一直受到阻碍。然而，长时间进化过程中的结构保守创造了一种独特的替代模式，这种模式可以随着比较基因组学的出现而被利用。作者设计了一种基于多重比对系统发育分析的鉴定功能RNA结构的方法。这种方法已经被用来筛选人类基因组中受到强烈选择性限制的区域。结果是一组48,479个候选RNA结构。对于某些已知的功能RNA，如miRNAs和组蛋白3‘UTR茎环，这个集合几乎包括所有高度保守的成员。最初的大量候选集已经按大小、形状和基因组位置进行了划分，并按得分进行了排序，以产生miRNAs、硒半胱氨酸插入位点、RNA编辑发夹和参与转录自动调节的RNA的特定候选列表。
The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed a general comparative genomics method based on phylogenetic stochastic context-free grammars for identifying functional RNAs encoded in the human genome and used it to survey an eight-way genome-wide alignment of the human, chimpanzee, mouse, rat, dog, chicken, zebra-fish, and puffer-fish genomes for deeply conserved functional RNAs. At a loose threshold for acceptance, this search resulted in a set of 48,479 candidate RNA structures. This screen finds a large number of known functional RNAs, including 195 miRNAs, 62 histone 3′UTR stem loops, and various types of known genetic recoding elements. Among the highest-scoring new predictions are 169 new miRNA candidates, as well as new candidate selenocysteine insertion sites, RNA editing hairpins, RNAs involved in transcript auto regulation, and many folds that form singletons or small functional RNA families of completely unknown function. While the rate of false positives in the overall set is difficult to estimate and is likely to be substantial, the results nevertheless provide evidence for many new human functional RNAs and present specific predictions to facilitate their further characterization. Structurally functional RNA is a versatile component of the cell that comprises both independent molecules and regulatory elements of mRNA transcripts. The many recent discoveries of functional RNAs, most notably miRNAs, suggests that many more are yet to be found. Computational identification of functional RNAs has traditionally been hampered by the lack of strong sequence signals. However, structural conservation over long evolutionary times creates a characteristic substitution pattern, which can be exploited with the advent of comparative genomics. The authors have devised a method for identification of functional RNA structures based on phylogenetic analysis of multiple alignments. This method has been used to screen the regions of the human genome that are under strong selective constraints. The result is a set of 48,479 candidate RNA structures. For some classes of known functional RNAs, such as miRNAs and histone 3′UTR stem loops, this set includes nearly all deeply conserved members. The initial large candidate set has been partitioned by size, shape, and genomic location and ranked by score to produce specific lists of top candidates for miRNAs, selenocysteine insertion sites, RNA editing hairpins, and RNAs involved in transcript auto regulation.
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影响因子：
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