A C. Elegans Genome-scale MicroRNA Network Contains Composite Feedback Motifs with High Flux Capacity

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2008 Sep 17

PMID 18794350

Citations 132

Authors

Natalia J Martinez

Maria C Ow

M Inmaculada Barrasa

Molly Hammell

Reynaldo Sequerra

Lynn Doucette-Stamm

Frederick P Roth

Victor R Ambros

Albertha J M Walhout

Affiliations

Soon will be listed here.

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.

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