Human MicroRNA targets.

Human MicroRNA targets.
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DOI:
10.1371/journal.pbio.0020363
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发表时间:
2004-11
期刊:
影响因子:
9.8
通讯作者:
Marks DS
Marks DS
中科院分区:
生物学1区
文献类型:
--
作者:
John B;Enright AJ;Aravin A;Tuschl T;Sander C;Marks DS

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微小RNA(miRNAs)在特定位点与靶mRNA相互作用以诱导信息的切割或抑制翻译。大多数哺乳动物miRNAs的具体功能尚不清楚。我们预测了目前已知的218种哺乳动物miRNAs在人类基因转录本3′端非翻译区的靶位点,以便于集中实验。我们报告了大约2,000个在哺乳动物中具有保守的miRNA靶位点的人类基因,以及大约250个在哺乳动物和鱼类之间作为靶点保守的人类基因。预测算法使用位置特定的规则优化序列互补性,并依赖于物种间保守的严格要求。该方法的有效性的实验支持来自已知的目标和预测的目标在哺乳动物中与脆性X智力低下蛋白相关的mRNA中的强烈富集。这与miRNA在核糖核颗粒与转录调控信息相互作用中充当序列特异性衔接子的假设一致。过度代表的靶点组包括编码转录因子的mRNA、miRNA机制的组分和参与翻译调控的其他蛋白质,以及代表基因调控中的新反馈环的泛素机制的组分。有关靶基因、靶过程和靶预测开源软件(米兰达)的详细信息可在http://www.microrna.org上获得。我们的分析表明,约占所有人类基因1%的miRNA基因调节10%或更多的人类基因的蛋白质产生。这项计算分析提供了证据,表明多达10%的人类基因是被称为microRNA的小RNA分子调节的目标
MicroRNAs (miRNAs) interact with target mRNAs at specific sites to induce cleavage of the message or inhibit translation. The specific function of most mammalian miRNAs is unknown. We have predicted target sites on the 3′ untranslated regions of human gene transcripts for all currently known 218 mammalian miRNAs to facilitate focused experiments. We report about 2,000 human genes with miRNA target sites conserved in mammals and about 250 human genes conserved as targets between mammals and fish. The prediction algorithm optimizes sequence complementarity using position-specific rules and relies on strict requirements of interspecies conservation. Experimental support for the validity of the method comes from known targets and from strong enrichment of predicted targets in mRNAs associated with the fragile X mental retardation protein in mammals. This is consistent with the hypothesis that miRNAs act as sequence-specific adaptors in the interaction of ribonuclear particles with translationally regulated messages. Overrepresented groups of targets include mRNAs coding for transcription factors, components of the miRNA machinery, and other proteins involved in translational regulation, as well as components of the ubiquitin machinery, representing novel feedback loops in gene regulation. Detailed information about target genes, target processes, and open-source software for target prediction (miRanda) is available at http://www.microrna.org. Our analysis suggests that miRNA genes, which are about 1% of all human genes, regulate protein production for 10% or more of all human genes. This computational analysis provides evidence that as many as 10% of human genes are targets for regulation by small RNA molecules called microRNAs
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