Chan Chang S, Elemento Olivier, Tavazoie Saeed
Department of Molecular Biology and The Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
PLoS Comput Biol. 2005 Dec;1(7):e69. doi: 10.1371/journal.pcbi.0010069. Epub 2005 Dec 9.
We used network-level conservation between pairs of fly (Drosophila melanogaster/D. pseudoobscura) and worm (Caenorhabditis elegans/C. briggsae) genomes to detect highly conserved mRNA motifs in 3' untranslated regions. Many of these elements are complementary to the 5' extremity of known microRNAs (miRNAs), and likely correspond to their target sites. We also identify known targets of RNA-binding proteins, and many novel sites not yet known to be functional. Coherent sets of genes with similar function often bear the same conserved elements, providing new insights into their cellular functions. We also show that target sites for distinct miRNAs are often simultaneously conserved, suggesting combinatorial regulation by multiple miRNAs. A genome-wide search for conserved stem-loops, containing complementary sequences to the novel sites, revealed many new candidate miRNAs that likely target them. We also provide evidence that posttranscriptional networks have undergone extensive rewiring across distant phyla, despite strong conservation of regulatory elements themselves.
我们利用果蝇（黑腹果蝇/拟暗果蝇）和线虫（秀丽隐杆线虫/briggsae线虫）基因组对之间的网络水平保守性，来检测3'非翻译区中高度保守的mRNA基序。这些元件中的许多与已知微小RNA（miRNA）的5'末端互补，并且可能对应于它们的靶位点。我们还鉴定了RNA结合蛋白的已知靶标，以及许多尚未知具有功能的新位点。具有相似功能的相关基因集通常带有相同的保守元件，这为它们的细胞功能提供了新的见解。我们还表明，不同miRNA的靶位点通常同时保守，这表明多个miRNA进行组合调控。全基因组搜索包含与新位点互补序列的保守茎环，揭示了许多可能靶向它们的新候选miRNA。我们还提供证据表明，尽管调控元件本身具有很强的保守性，但转录后网络在不同的门中已经经历了广泛的重新布线。
