A C. elegans genome-scale microRNA network contains composite feedback motifs with high flux capacity

Martinez, N. J., Ow, M. C., Barrasa, M. I., Hammell, M., Sequerra, R., Doucette-Stamm, L., Roth, F. P., Ambros, V. R., Walhout, A. J. (September 2008) A C. elegans genome-scale microRNA network contains composite feedback motifs with high flux capacity. Genes & Development, 22 (18). pp. 2535-49. ISSN 0890-9369 (Print)0890-9369

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URL: http://www.ncbi.nlm.nih.gov/pubmed/18794350
DOI: 10.1101/gad.1678608

Abstract

MicroRNAs (miRNAs) and transcription factors (TFs) are primary metazoan gene regulators. Whereas much attention has focused on finding the targets of both miRNAs and TFs, the transcriptional networks that regulate miRNA expression remain largely unexplored. Here, we present the first genome-scale Caenorhabditis elegans miRNA regulatory network that contains experimentally mapped transcriptional TF --> miRNA interactions, as well as computationally predicted post-transcriptional miRNA --> TF interactions. We find that this integrated miRNA network contains 23 miRNA <--> TF composite feedback loops in which a TF that controls a miRNA is itself regulated by that same miRNA. By rigorous network randomizations, we show that such loops occur more frequently than expected by chance and, hence, constitute a genuine network motif. Interestingly, miRNAs and TFs in such loops are heavily regulated and regulate many targets. This "high flux capacity" suggests that loops provide a mechanism of high information flow for the coordinate and adaptable control of miRNA and TF target regulons.

Item Type: Paper
Uncontrolled Keywords: Animals Animals, Genetically Modified Caenorhabditis elegans/embryology/*genetics *Genome MicroRNAs/*genetics Polymerase Chain Reaction Transcription, Genetic
Subjects: organism description > animal > C elegans
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
CSHL Authors:
Communities: CSHL labs > Hammell M. lab
Depositing User: Matt Covey
Date: 15 September 2008
Date Deposited: 06 Nov 2014 17:58
Last Modified: 06 Nov 2014 17:58
PMCID: PMC2546694
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30883

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