Chen K, Rajewsky N
Center for Comparative Functional Genomics, Department of Biology, New York University, New York, New York 10003, USA.
Cold Spring Harb Symp Quant Biol. 2006;71:149-56. doi: 10.1101/sqb.2006.71.039.
microRNAs (miRNAs) are a class of small noncoding RNAs that posttranscriptionally regulate a large fraction of genes in animal genomes. We have previously published computational miRNA target predictions in five vertebrates, six flies, and three nematodes. Here, we report a comprehensive study of the "deep" conservation of miRNA targets and conserved 3'UTR (untranslated region) motifs in general across vertebrates, flies, and nematodes. Our data indicate that although many miRNA genes and 3'UTR motifs are well-conserved, miRNA-target relationships have diverged more rapidly, and we explicitly assign each gained or lost miRNA-target relationship to one of the three clades. However, we also identify a small but significant number of deeply conserved miRNA targets and show that these are enriched for essential processes related to development. Finally, we provide lists of 3'UTR motifs that are significantly conserved, and thus likely functional, classified by their distribution in the three clades. We find hundreds of such motifs specific to each clade, dozens specific to each pair of clades, and ten shared by vertebrates, flies, and nematodes. These findings suggest that posttranscriptional control has undergone extensive rewiring during metazoan evolution and that many deeply conserved miRNA-target relationships may be vital subunits of metazoan gene regulatory networks.
微小RNA(miRNA)是一类小的非编码RNA,它们在转录后水平上调控动物基因组中很大一部分基因。我们之前已经发表了在五种脊椎动物、六种果蝇和三种线虫中对miRNA靶标的计算预测。在此,我们报告了一项关于miRNA靶标和保守的3'非翻译区(UTR)基序在脊椎动物、果蝇和线虫中普遍存在的“深度”保守性的综合研究。我们的数据表明,尽管许多miRNA基因和3'UTR基序高度保守,但miRNA - 靶标关系的分化更为迅速,并且我们明确地将每个获得或丢失的miRNA - 靶标关系归属于三个进化分支之一。然而,我们也鉴定出少量但数量可观的深度保守的miRNA靶标,并表明这些靶标在与发育相关的基本过程中富集。最后,我们提供了按其在三个进化分支中的分布分类的显著保守且可能具有功能的3'UTR基序列表。我们发现每个进化分支有数百个这样的基序,每对进化分支有数十个,以及脊椎动物、果蝇和线虫共有的十个。这些发现表明,转录后调控在后生动物进化过程中经历了广泛的重新布线,并且许多深度保守的miRNA - 靶标关系可能是后生动物基因调控网络的重要亚单位。
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