title: Combinatorial microRNA target predictions.
abstract: 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 transcript. 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.
authors.affiliation: Center for Comparative Functional Genomics, Department of Biology, New York University, 100 Washington Square East, New York, New York 10003, USA.
authors.forename: Azra
authors.initials: A
authors.lastname: Krek
authors.forename: Dominic
authors.initials: D
authors.lastname: Grün
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Poy
authors.forename: Rachel
authors.initials: R
authors.lastname: Wolf
authors.forename: Lauren
authors.initials: L
authors.lastname: Rosenberg
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Epstein
authors.forename: Philip
authors.initials: P
authors.lastname: MacMenamin
authors.forename: Isabelle
authors.initials: I
authors.lastname: da Piedade
authors.forename: Kristin C
authors.initials: KC
authors.lastname: Gunsalus
authors.forename: Markus
authors.initials: M
authors.lastname: Stoffel
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Rajewsky
mesh_terms: D000465:Algorithms; D000818:Animals; D019295:Computational Biology; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: D035683:MicroRNAs