revealing posttranscriptional regulatory elements through network-level conservation通过网络级保护揭示转录后的调控元件.pdfVIP

Revealing Posttranscriptional Regulatory Elements Through Network-Level Conservation [ [ * Chang S. Chan , Olivier Elemento , Saeed Tavazoie Department of Molecular Biology and The Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America 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 39 untranslated regions. Many of these elements are complementary to the 59 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. Citation: Chan CS, Elemento O, Tavazoie S (2005) Revealing posttranscriptional regulatory elements through network-level conservation. PLoS Comput Biol 1(7): e69. While hundreds of animal miRNAs have been discovered Introduction [7], it is likely that many more have not, probab