title: MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals.
abstract: MicroRNAs (miRNAs) are regulatory molecules that participate in diverse biological processes in animals and plants. While thousands of mammalian genes are potentially targeted by miRNAs, the functions of miRNAs in the context of gene networks are not well understood. Specifically, it is unknown whether miRNA-containing networks have recurrent circuit motifs, as has been observed in regulatory networks of bacteria and yeast. Here we develop a computational method that utilizes gene expression data to show that two classes of circuits-corresponding to positive and negative transcriptional coregulation of a miRNA and its targets-are prevalent in the human and mouse genomes. Additionally, we find that neuronal-enriched miRNAs tend to be coexpressed with their target genes, suggesting that these miRNAs could be involved in neuronal homeostasis. Our results strongly suggest that coordinated transcriptional and miRNA-mediated regulation is a recurrent motif to enhance the robustness of gene regulation in mammalian genomes.
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: John
authors.initials: J
authors.lastname: Tsang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
mesh_terms: D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D030541:Databases, Genetic; D005246:Feedback; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008957:Models, Genetic; D009415:Nerve Net / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D035683:MicroRNAs