Nature Genetics37, 495 - 500 (2005)
Published online: 3 April 2005; | doi:10.1038/ng1536
Combinatorial microRNA target predictions
Azra Krek1, 2, 4, Dominic Grün1, 4, Matthew N Poy3, 4, Rachel Wolf1, Lauren Rosenberg1, Eric J Epstein3, Philip MacMenamin1, Isabelle da Piedade1, Kristin C Gunsalus1, Markus Stoffel3
& Nikolaus Rajewsky1
1
Center for Comparative Functional Genomics, Department of Biology, New York University, 100 Washington Square East, New York, New York 10003, USA.
2
Department of Physics, New York University, New York, New York 10003, USA.
3
Laboratory of Metabolic Diseases, The Rockefeller University, New York, New York 10021, USA.
MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3' untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript1,
2,
3. Different combinations of microRNAs are expressed in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published microRNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results suggest widespread coordinate control executed by microRNAs. In particular, we experimentally validate common regulation of Mtpn by miR-375, miR-124 and let-7b and thus provide evidence for coordinate microRNA control in mammals.
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