A genome-wide map of conserved microRNA targets in C. elegans
A genome-wide map of conserved microRNA targets in C. elegans
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DOI：
10.1016/j.cub.2006.01.050
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发表时间：
2006-03-07
期刊：
影响因子：
9.2
通讯作者：
Rajewsky, N
中科院分区：
文献类型：
--
作者：
Lall, S;Grün, D;Rajewsky, N
背景：后生动物miRNAs通过结合同源mRNA的3' UTR来调节蛋白质编码基因。确定115种已知C.结果：通过使用新版本的PicTar和三种线虫的序列比对，我们预测miRNAs至少调控线虫10%的功能。elegans基因通过保守的相互作用。我们已经开发了一种新的实验管道，通过适合高通量克隆的内源性报告基因表达系统来测定3'UTR介导的转录后基因调控，证明了该系统使用最深入研究的miRNA之一let-7的实用性。我们的表达分析揭示了几个新的潜在let-7靶点，并提出了一个新的let-7活动在头部肌肉和神经元。为了探索miRNA功能的全基因组趋势，我们分析了预测的靶基因的功能类别，发现三分之一的C。elegans miRNAs靶基因组富集了特定的功能注释。我们还将miRNA靶点预测与C.结论：至少有10%的C.线虫基因是预测的miRNA靶标，并且许多线虫miRNA似乎通过靶向功能相关的基因来调节生物过程。我们还开发并成功地利用了一种体内系统，用于在可能的内源性表达结构域中测试miRNA靶标预测。数千个线虫、人类和苍蝇的全基因组miRNA靶点预测可从PicTar网站获得，并链接到可访问的图形网络浏览工具，允许在各种功能基因组数据资源的背景下探索miRNA靶点预测。
Background: Metazoan miRNAs regulate proteincoding genes by binding the 3' UTR of cognate mRNAs. Identifying targets for the 115 known C. elegans miRNAs is essential for understanding their function.Results: By using a new version of PicTar and sequence alignments of three nematodes, we predict that miRNAs regulate at least 10% of C. elegans genes through conserved interactions. We have developed a new experimental pipeline to assay 3' UTR-mediated posttranscriptional gene regulation via an endogenous reporter expression system amenable to high-throughput cloning, demonstrating the utility of this system using one of the most intensely studied miRNAs, let-7. Our expression analyses uncover several new potential let-7 targets and suggest a new let-7 activity in head muscle and neurons. To explore genome-wide trends in miRNA function, we analyzed functional categories of predicted target genes, finding that one-third of C. elegans miRNAs target gene sets are enriched for specific functional annotations. We have also integrated miRNA target predictions with other functional genomic data from C. elegans.Conclusions: At least 10% of C. elegans genes are predicted miRNA targets, and a number of nematode miRNAs seem to regulate biological processes by targeting functionally related genes. We have also developed and successfully utilized an in vivo system for testing miRNA target predictions in likely endogenous expression domains. The thousands of genome-wide miRNA target predictions for nematodes, humans, and flies are available from the PicTar website and are linked to an accessible graphical network-browsing tool allowing exploration of miRNA target predictions in the context of various functional genomic data resources.